Trial Watch: Peptide vaccines in cancer therapy

OncoImmunology

Volumn 2, Issue 12, 2013, Pages 1-11

  Aranda, Fernando ^a,b,c,d   Vacchelli, Erika ^a,b,c,d   Eggermont, Alexander ^a   Galon, Jerome ^b,d,e,f   Sautès Fridman, Catherine ^b,d,f   Tartour, Eric ^b,g   Zitvogel, Laurence ^a,b   Kroemer, Guido ^b,d,e,g,h   Galluzzi, Lorenzo ^a,d,e  

^a INSTITUT GUSTAVE ROUSSY   (France)

^b INSERM   (France)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d CENTRE DE RECHERCHE DES CORDELIERS   (France)

^e UNIVERSITÉ PARIS DESCARTES   (France)

^f SORBONNE UNIVERSITÉ   (France)

^g HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^h Metabolomics Platform   (France)

Author keywords

Adjuvants; Dendritic cells; Ipilimumab; NY ESO 1; Survivin; TLR agonists

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; HLA A2 ANTIGEN; INDOLEAMINE 2,3 DIOXYGENASE DERIVED PEPTIDE VACCINE; INSULIN RECEPTOR SUBSTRATE 2; MELAN A; MUCIN 1; NY ESO 1 ANTIGEN; PEPTIDE VACCINE; TELOMERASE REVERSE TRANSCRIPTASE; TUMOR ANTIGEN; UNCLASSIFIED DRUG; WT1 PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANTIGEN SPECIFICITY; BREAST CARCINOMA; CANCER IMMUNIZATION; CANCER PREVENTION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; ERYTHEMA; GLIOBLASTOMA; HUMAN; HYPERTENSION; IMMUNOLOGICAL TOLERANCE; IMMUNOSTIMULATION; INJECTION SITE INDURATION; LUNG NON SMALL CELL CANCER; MELANOMA; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; NONHUMAN; PROSTATE CANCER; PROTEINURIA; REVIEW; TUMOR IMMUNITY;

EID: 84894553314     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/onci.26621     Document Type: Review

References (172)

1. Waldmann TA. Immunotherapy: past, present and future. Nat Med 2003; 9:269-77; PMID:12612576; http://dx.doi.org/10.1038/nm0303-269
2. Riedel S. Edward Jenner and the history of smallpox and vaccination. [Bayl Univ Med Cent]. Proc (Bayl Univ Med Cent) 2005; 18:21-5; PMID:16200144
3. Smith KA. Edward jenner and the small pox vaccine. Front Immunol 2011; 2:21; PMID:22566811; http:// dx.doi.org/10.3389/fimmu.2011.00021
4. Smith KA. Louis pasteur, the father of immunology? Front Immunol 2012; 3:68; PMID:22566949; http://dx.doi.org/10.3389/fimmu.2012.00068
5. Breman JG, Arita I. The confirmation and maintenance of smallpox eradication. N Engl J Med 1980; 303:1263-73; PMID:6252467; http://dx.doi. org/10.1056/NEJM198011273032204
6. Vacchelli E, Martins I, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Peptide vaccines in cancer therapy. Oncoimmunology 2012; 1:1557-76; PMID:23264902; http://dx.doi.org/10.4161/ onci.22428
7. Galluzzi L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1:699-716; PMID:22934262; http://dx.doi. org/10.4161/onci.20696
8. Vacchelli E, Galluzzi L, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial watch: FDAapproved Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1:894-907; PMID:23162757; http://dx.doi.org/10.4161/ onci.20931
9. Vacchelli E, Eggermont A, Sautès-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Toll-like receptor agonists for cancer therapy. Oncoimmunology 2013; 2:e25238; PMID:24083080; http://dx.doi.org/10.4161/ onci.25238
10. Oblak A, Jerala R. Toll-like receptor 4 activation in cancer progression and therapy. Clin Dev Immunol 2011; 2011:609579; PMID:22110526; http://dx.doi. org/10.1155/2011/609579
11. Burgio GR. Commentary on the biological self: Toward a "Biological Ego". From Garrod's "chemical individuality" to Burnet's "self ". Thymus 1990; 16:99-117; PMID:2256127
12. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12:991-1045; PMID:8011301; http://dx.doi.org/10.1146/annurev. iy.12.040194.005015
13. Matzinger P. The danger model: a renewed sense of self. Science 2002; 296:301-5; PMID:11951032; http://dx.doi.org/10.1126/science.1071059
14. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254:1643-7; PMID:1840703; http://dx.doi. org/10.1126/science.1840703
15. Parmiani G. Tumor immunity as autoimmunity: tumor antigens include normal self proteins which stimulate anergic peripheral T cells. Immunol Today 1993; 14:536-8; PMID:8274196; http://dx.doi. org/10.1016/0167-5699(93)90183-L
16. Galluzzi L, Senovilla L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology 2012; 1:1111-34; PMID:23170259; http://dx.doi.org/10.4161/ onci.21494
17. Vacchelli E, Vitale I, Eggermont A, Fridman WH, Fucíková J, Cremer I, et al. Trial Watch: Dendritic cell-based interventions for cancer therapy. OncoImmunology 2013; 2:e25771; PMID:23170259; http://dx.doi.org/10.4161/ onci.25771
18. Senovilla L, Vacchelli E, Garcia P, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: DNA vaccines for cancer therapy. Oncoimmunology 2013; 2:e23803; PMID:23734328; http://dx.doi.org/10.4161/ onci.23803
19. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 2004; 199:815-24; PMID:15024047; http://dx.doi. org/10.1084/jem.20032220
20. Kreutz M, Tacken PJ, Figdor CG. Targeting dendritic cells--why bother? Blood 2013; 121:2836-44; PMID:23390195; http://dx.doi.org/10.1182/ blood-2012-09-452078
21. Tacken PJ, de Vries IJ, Torensma R, Figdor CG. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 2007; 7:790-802; PMID:17853902; http://dx.doi.org/10.1038/ nri2173
22. Agosti JM, Goldie SJ. Introducing HPV vaccine in developing countries--key challenges and issues. N Engl J Med 2007; 356:1908-10; PMID:17494923; http://dx.doi.org/10.1056/NEJMp078053
23. Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, et al.; HPV PATRICIA Study Group. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a doubleblind, randomised study in young women. Lancet 2009; 374:301-14; PMID:19586656; http://dx.doi. org/10.1016/S0140-6736(09)61248-4
24. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007; 356:1915-27; PMID:17494925; http://dx.doi.org/10.1056/ NEJMoa061741
25. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, et al.; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363:411-22; PMID:20818862; http://dx.doi.org/10.1056/ NEJMoa1001294
26. Galluzzi L. New immunotherapeutic paradigms for castration-resistant prostate cancer. OncoImmunology 2013; 2:e26084; http://dx.doi. org/10.4161/onci.26084
27. Bergman PJ, Camps-Palau MA, McKnight JA, Leibman NF, Craft DM, Leung C, Liao J, Riviere I, Sadelain M, Hohenhaus AE, et al. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006; 24:4582-5; PMID:16188351; http:// dx.doi.org/10.1016/j.vaccine.2005.08.027
28. Bergman PJ, McKnight J, Novosad A, Charney S, Farrelly J, Craft D, Wulderk M, Jeffers Y, Sadelain M, Hohenhaus AE, et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res 2003; 9:1284-90; PMID:12684396
29. Liao JC, Gregor P, Wolchok JD, Orlandi F, Craft D, Leung C, Houghton AN, Bergman PJ. Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma. Cancer Immun 2006; 6:8; PMID:16626110
30. USDA licenses DNA vaccine for treatment of melanoma in dogs. J Am Vet Med Assoc 2010; 236:495; PMID:20187810
31. Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 2008; 8:351-60; PMID:18418403; http://dx.doi.org/10.1038/ nrc2373
32. Nizard M, Sandoval F, Badoual C, Pere H, Terme M, Hans S, Benhamouda N, Granier C, Brasnu D, Tartour E. Immunotherapy of HPV-associated head and neck cancer: Critical parameters. Oncoimmunology 2013; 2:e24534; PMID:23894716; http://dx.doi. org/10.4161/onci.24534
33. Sandoval F, Terme M, Nizard M, Badoual C, Bureau MF, Freyburger L, Clement O, Marcheteau E, Gey A, Fraisse G, et al. Mucosal imprinting of vaccineinduced CD8+ T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med 2013; 5:172ra20; PMID:23408053; http://dx.doi.org/10.1126/ scitranslmed.3004888
34. Vacchelli E, Eggermont A, Fridman WH, Galon J, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2013; 2:e24238; PMID:23762803; http://dx.doi.org/10.4161/ onci.24238
35. Galluzzi L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial Watch: Adoptive cell transfer immunotherapy. Oncoimmunology 2012; 1:306-15; PMID:22737606; http://dx.doi.org/10.4161/ onci.19549
36. Vacchelli E, Vitale I, Tartour E, Eggermont A, Sautes-Fridman C, Galon J, et al. Trial Watch: Anticancer radioimmunotherapy. OncoImmunology 2013; 2: e24238; http://dx.doi.org/10.4161/onci.24238
37. Menger L, Vacchelli E, Kepp O, Eggermont A, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Cardiac glycosides and cancer therapy. Oncoimmunology 2013; 2:e23082; PMID:23525565; http://dx.doi.org/10.4161/ onci.23082
38. Vacchelli E, Eggermont A, Sautès-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Oncolytic viruses for cancer therapy. Oncoimmunology 2013; 2:e24612; PMID:23894720; http://dx.doi.org/10.4161/ onci.24612
39. Senovilla L, Vacchelli E, Galon J, Adjemian S, Eggermont A, Fridman WH, Sautès-Fridman C, Ma Y, Tartour E, Zitvogel L, et al. Trial watch: Prognostic and predictive value of the immune infiltrate in cancer. Oncoimmunology 2012; 1:1323-43; PMID:23243596; http://dx.doi.org/10.4161/ onci.22009
40. Crane CA, Han SJ, Ahn B, Oehlke J, Kivett V, Fedoroff A, Butowski N, Chang SM, Clarke J, Berger MS, et al. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res 2013; 19:205-14; PMID:22872572; http://dx.doi. org/10.1158/1078-0432.CCR-11-3358
41. Salerno EP, Shea SM, Olson WC, Petroni GR, Smolkin ME, McSkimming C, Chianese-Bullock KA, Slingluff CL Jr. Activation, dysfunction and retention of T cells in vaccine sites after injection of incomplete Freund's adjuvant, with or without peptide. Cancer Immunol Immunother 2013; 62:1149-59; PMID:23657629; http://dx.doi.org/10.1007/ s00262-013-1435-5
42. Zeestraten EC, Speetjens FM, Welters MJ, Saadatmand S, Stynenbosch LF, Jongen R, Kapiteijn E, Gelderblom H, Nijman HW, Valentijn AR, et al. Addition of interferon-a to the p53-SLP® vaccine results in increased production of interferon-? in vaccinated colorectal cancer patients: a phase I/II clinical trial. Int J Cancer 2013; 132:1581-91; PMID:22948952; http://dx.doi.org/10.1002/ ijc.27819
43. Tada Y, Yoshikawa T, Shimomura M, Sawada Y, Sakai M, Shirakawa H, Nobuoka D, Nakatsura T. Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican3derived peptide. Int J Oncol 2013; 43:1019-26; PMID:23903757
44. Okamoto I, Arao T, Miyazaki M, Satoh T, Okamoto K, Tsunoda T, Nishio K, Nakagawa K. Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Cancer Sci 2012; 103:2135-8; PMID:22957712; http://dx.doi.org/10.1111/ cas.12014
45. Sugiura F, Inoue K, Okuno K, Sukegawa Y. [Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer]. Gan To Kagaku Ryoho 2012; 39:1760-2; PMID:23267878
46. Sonpavde G, Wang M, Peterson LE, Wang HY, Joe T, Mims MP, Kadmon D, Ittmann MM, Wheeler TM, Gee AP, et al. HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer. Invest New Drugs 2013; Forthcoming; PMID:23609828; http://dx.doi. org/10.1007/s10637-013-9960-9
47. Kameshima H, Tsuruma T, Kutomi G, Shima H, Iwayama Y, Kimura Y, Imamura M, Torigoe T, Takahashi A, Hirohashi Y, et al. Immunotherapeutic benefit of a-interferon (IFNa) in survivin2Bderived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci 2013; 104:124-9; PMID:23078230; http://dx.doi.org/10.1111/ cas.12046
48. Eikawa S, Kakimi K, Isobe M, Kuzushima K, Luescher I, Ohue Y, Ikeuchi K, Uenaka A, Nishikawa H, Udono H, et al. Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide. Int J Cancer 2013; 132:345-54; PMID:22729530; http://dx.doi. org/10.1002/ijc.27682
49. Fenoglio D, Traverso P, Parodi A, Tomasello L, Negrini S, Kalli F, Battaglia F, Ferrera F, Sciallero S, Murdaca G, et al. A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer. Cancer Immunol Immunother 2013; 62:1041-52; PMID:23591981; http://dx.doi.org/10.1007/ s00262-013-1415-9
50. Filipazzi P, Pilla L, Mariani L, Patuzzo R, Castelli C, Camisaschi C, Maurichi A, Cova A, Rigamonti G, Giardino F, et al. Limited induction of tumor crossreactive T cells without a measurable clinical benefit in early melanoma patients vaccinated with human leukocyte antigen class I-modified peptides. Clin Cancer Res 2012; 18:6485-96; PMID:23032742; http://dx.doi.org/10.1158/1078-0432.CCR-12-1516
51. Kono K, Iinuma H, Akutsu Y, Tanaka H, Hayashi N, Uchikado Y, Noguchi T, Fujii H, Okinaka K, Fukushima R, et al. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med 2012; 10:141; PMID:22776426; http://dx.doi. org/10.1186/1479-5876-10-141
52. Suzuki H, Fukuhara M, Yamaura T, Mutoh S, Okabe N, Yaginuma H, Hasegawa T, Yonechi A, Osugi J, Hoshino M, et al. Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer. J Transl Med 2013; 11:97; PMID:23578144; http://dx.doi. org/10.1186/1479-5876-11-97
53. Matsushita N, Aruga A, Inoue Y, Kotera Y, Takeda K, Yamamoto M. Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncol Rep 2013; 29:951-9; PMID:23314271
54. Yoshimura K, Minami T, Nozawa M, Uemura H. Phase I clinical trial of human vascular endothelial growth factor receptor 1 peptide vaccines for patients with metastatic renal cell carcinoma. Br J Cancer 2013; 108:1260-6; PMID:23470466; http://dx.doi. org/10.1038/bjc.2013.90
55. Ishikawa H, Imano M, Shiraishi O, Yasuda A, Peng YF, Shinkai M, Yasuda T, Imamoto H, Shiozaki H. Phase I clinical trial of vaccination with LY6Kderived peptide in patients with advanced gastric cancer. Gastric Cancer 2013; Forthcoming; PMID:23613128; http://dx.doi.org/10.1007/ s10120-013-0258-6
56. Sawada Y, Yoshikawa T, Nobuoka D, Shirakawa H, Kuronuma T, Motomura Y, Mizuno S, Ishii H, Nakachi K, Konishi M, et al. Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival. Clin Cancer Res 2012; 18:3686-96; PMID:22577059; http:// dx.doi.org/10.1158/1078-0432.CCR-11-3044
57. Hayashi H, Kurata T, Fujisaka Y, Kawakami H, Tanaka K, Okabe T, Takeda M, Satoh T, Yoshida K, Tsunoda T, et al. Phase I trial of OTS11101, an antiangiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor. Cancer Sci 2013; 104:98-104; PMID:23020774; http://dx.doi. org/10.1111/cas.12034
58. Sabbatini P, Tsuji T, Ferran L, Ritter E, Sedrak C, Tuballes K, Jungbluth AA, Ritter G, Aghajanian C, Bell-McGuinn K, et al. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res 2012; 18:6497-508; PMID:23032745; http://dx.doi. org/10.1158/1078-0432.CCR-12-2189
59. Takahashi R, Ishibashi Y, Hiraoka K, Matsueda S, Kawano K, Kawahara A, Kage M, Ohshima K, Yamanaka R, Shichijo S, et al. Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients. Cancer Sci 2013; Forthcoming; PMID:23829867; http://dx.doi. org/10.1111/cas.12226
60. Sawada Y, Yoshikawa T, Fujii S, Mitsunaga S, Nobuoka D, Mizuno S, et al. Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination: An autopsy case. Hum Vaccin Immunother 2013; Forthcoming; PMID:23466818; http://dx.doi. org/10.4161/hv.24179
61. Becker JC, Andersen MH, Hofmeister-Müller V, Wobser M, Frey L, Sandig C, Walter S, Singh-Jasuja H, Kämpgen E, Opitz A, et al. Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma. Cancer Immunol Immunother 2012; 61:2091-103; PMID:22565484; http://dx.doi. org/10.1007/s00262-012-1266-9
62. Bloom JE, McNeel DG, Olson BM. Vaccination using peptides spanning the SYT-SSX tumor-specific translocation. Expert Rev Vaccines 2012; 11:1401-4; PMID:23252384; http://dx.doi.org/10.1586/ erv.12.122
63. Miyatake T, Ueda Y, Morimoto A, Enomoto T, Nishida S, Shirakata T, Oka Y, Tsuboi A, Oji Y, Hosen N, et al. WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial. J Cancer Res Clin Oncol 2013; 139:457-63; PMID:23160854; http://dx.doi. org/10.1007/s00432-012-1348-2
64. Miller LH, Saul A, Mahanty S. Revisiting Freund's incomplete adjuvant for vaccines in the developing world. Trends Parasitol 2005; 21:412-4; PMID:16043410; http://dx.doi.org/10.1016/j. pt.2005.07.005
65. Jensen FC, Savary JR, Diveley JP, Chang JC. Adjuvant activity of incomplete Freund's adjuvant. Adv Drug Deliv Rev 1998; 32:173-86; PMID:10837643; http://dx.doi.org/10.1016/S0169-409X(98)00009-X
66. Murad YM, Clay TM, Lyerly HK, Morse MA. CPG-7909 (PF-3512676, ProMune): toll-like receptor-9 agonist in cancer therapy. Expert Opin Biol Ther 2007; 7:1257-66; PMID:17696823; http://dx.doi. org/10.1517/14712598.7.8.1257
67. Ashkar AA, Rosenthal KL. Toll-like receptor 9, CpG DNA and innate immunity. Curr Mol Med 2002; 2:545-56; PMID:12243247; http://dx.doi. org/10.2174/1566524023362159
68. Ming Lim C, Stephenson R, Salazar AM, Ferris RL. TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR(+) head and neck cancer cells. Oncoimmunology 2013; 2:e24677; PMID:23894722; http://dx.doi.org/10.4161/ onci.24677
69. Chew V, Abastado JP. Immunomodulation of the tumor microenvironment by Toll-like receptor-3 (TLR3) ligands. Oncoimmunology 2013; 2:e23493; PMID:23734310; http://dx.doi.org/10.4161/ onci.23493
70. Smits EL, Anguille S, Berneman ZN. Interferon a may be back on track to treat acute myeloid leukemia. Oncoimmunology 2013; 2:e23619; PMID:23734314; http://dx.doi.org/10.4161/ onci.23619
71. Chen LL, Gouw L, Sabripour M, Hwu WJ, Benjamin RS. Combining targeted therapy with immunotherapy (interferon-a): Rational, efficacy in gastrointestinal stromal tumor model and implications in other malignancies. Oncoimmunology 2012; 1:773-6; PMID:22934279; http://dx.doi.org/10.4161/ onci.19729
72. Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Immunostimulatory cytokines. Oncoimmunology 2013; 2:e24850; PMID:24073369; http://dx.doi. org/10.4161/onci.24850
73. Vacchelli E, Galluzzi L, Eggermont A, Galon J, Tartour E, Zitvogel L, Kroemer G. Trial Watch: Immunostimulatory cytokines. Oncoimmunology 2012; 1:493-506; PMID:22754768; http://dx.doi. org/10.4161/onci.20459
74. Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret al.y: immunostimulation by anticancer drugs. Nat Rev Drug Discov 2012; 11:215-33; PMID:22301798; http://dx.doi.org/10.1038/ nrd3626
75. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013; 39:74-88; PMID:23890065; http://dx.doi.org/10.1016/j.immuni.2013.06.014
76. Vacchelli E, Galluzzi L, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Kroemer G. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2012; 1:179-88; PMID:22720239; http://dx.doi.org/10.4161/ onci.1.2.19026
77. Vacchelli E, Senovilla L, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2013; 2:e23510; PMID:23687621; http://dx.doi.org/10.4161/ onci.23510
78. Lai JP, Rosenberg AZ, Miettinen MM, Lee CC. NY-ESO-1 expression in sarcomas: A diagnostic marker and immunotherapy target. Oncoimmunology 2012; 1:1409-10; PMID:23243610; http://dx.doi. org/10.4161/onci.21059
79. Vitale I, Senovilla L, Jemaà M, Michaud M, Galluzzi L, Kepp O, Nanty L, Criollo A, Rello-Varona S, Manic G, et al. Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos. EMBO J 2010; 29:1272-84; PMID:20186124; http://dx.doi. org/10.1038/emboj.2010.11
80. Matsuda R, Enokida H, Chiyomaru T, Kikkawa N, Sugimoto T, Kawakami K, Tatarano S, Yoshino H, Toki K, Uchida Y, et al. LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling. Br J Cancer 2011; 104:376-86; PMID:21063397; http://dx.doi.org/10.1038/ sj.bjc.6605990
81. Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, et al. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res 2007; 67:11601-11; PMID:18089789; http://dx.doi.org/10.1158/0008-5472.CAN-07-3243
82. Sitnikova L, Mendese G, Liu Q, Woda BA, Lu D, Dresser K, Mohanty S, Rock KL, Jiang Z. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res 2008; 14:1701-6; PMID:18347170; http://dx.doi.org/10.1158/1078-0432.CCR-07-2039
83. Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, Li C, Chen W, Duan HO, McDougal S, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol 2006; 7:556-64; PMID:16814207; http://dx.doi.org/10.1016/ S1470-2045(06)70732-X
84. Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 2012; 488:665-9; PMID:22895187; http://dx.doi.org/10.1038/ nature11308
85. Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 2012; 485:195-200; PMID:22575959; http://dx.doi.org/10.1038/ nature11019
86. Uchida N, Tsunoda T, Wada S, Furukawa Y, Nakamura Y, Tahara H. Ring finger protein 43 as a new target for cancer immunotherapy. Clin Cancer Res 2004; 10:8577-86; PMID:15623641; http:// dx.doi.org/10.1158/1078-0432.CCR-04-0104
87. Aleskandarany MA, Negm OH, Rakha EA, Ahmed MA, Nolan CC, Ball GR, Caldas C, Green AR, Tighe PJ, Ellis IO. TOMM34 expression in early invasive breast cancer: a biomarker associated with poor outcome. Breast Cancer Res Treat 2012; 136:419-27; PMID:23053644; http://dx.doi.org/10.1007/ s10549-012-2249-4
88. Shimokawa T, Matsushima S, Tsunoda T, Tahara H, Nakamura Y, Furukawa Y. Identification of TOMM34, which shows elevated expression in the majority of human colon cancers, as a novel drug target. Int J Oncol 2006; 29:381-6; PMID:16820880
89. Komori H, Nakatsura T, Senju S, Yoshitake Y, Motomura Y, Ikuta Y, Fukuma D, Yokomine K, Harao M, Beppu T, et al. Identification of HLA-A2-or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma. Clin Cancer Res 2006; 12:2689-97; PMID:16675560; http://dx.doi.org/10.1158/1078-0432.CCR-05-2267
90. Nakatsura T, Komori H, Kubo T, Yoshitake Y, Senju S, Katagiri T, Furukawa Y, Ogawa M, Nakamura Y, Nishimura Y. Mouse homologue of a novel human oncofetal antigen, glypican-3, evokes T-cellmediated tumor rejection without autoimmune reactions in mice. Clin Cancer Res 2004; 10:8630-40; PMID:15623647; http://dx.doi.org/10.1158/1078-0432.CCR-04-1177
91. Rosenberg SA, Zhai Y, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Seipp CA, Einhorn JH, et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. J Natl Cancer Inst 1998; 90:1894-900; PMID:9862627
92. Overwijk WW, Tsung A, Irvine KR, Parkhurst MR, Goletz TJ, Tsung K, Carroll MW, Liu C, Moss B, Rosenberg SA, et al. gp100/pmel 17 is a murine tumor rejection antigen: induction of "self "-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. J Exp Med 1998; 188:277-86; PMID:9670040; http://dx.doi.org/10.1084/ jem.188.2.277
93. Zhai Y, Yang JC, Spiess P, Nishimura MI, Overwijk WW, Roberts B, Restifo NP, Rosenberg SA. Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100. J Immunother 1997; 20:15-25; PMID:9101410; http://dx.doi. org/10.1097/00002371-199701000-00002
94. Kawaguchi S, Tsukahara T, Ida K, Kimura S, Murase M, Kano M, Emori M, Nagoya S, Kaya M, Torigoe T, et al. SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group. Cancer Sci 2012; 103:1625-30; PMID:22726592; http:// dx.doi.org/10.1111/j.1349-7006.2012.02370.x
95. Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998; 338:153-60; PMID:9428816; http://dx.doi.org/10.1056/ NEJM199801153380303
96. Masuzawa T, Fujiwara Y, Okada K, Nakamura A, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Osawa R, et al. Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. Int J Oncol 2012; 41:1297-304; PMID:22842485
97. Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res 2006; 12:5841-9; PMID:17020992; http://dx.doi.org/10.1158/1078-0432.CCR-06-0750
98. Andersen MH, Svane IM, Becker JC, Straten PT. The universal character of the tumor-associated antigen survivin. Clin Cancer Res 2007; 13:5991-4; PMID:17947459; http://dx.doi.org/10.1158/1078-0432.CCR-07-0686
99. Schmidt SM, Schag K, Müller MR, Weck MM, Appel S, Kanz L, Grünebach F, Brossart P. Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells. Blood 2003; 102:571-6; PMID:12576330; http://dx.doi.org/10.1182/ blood-2002-08-2554
100. Pospori C, Xue SA, Holler A, Voisine C, Perro M, King J, Fallah-Arani F, Flutter B, Chakraverty R, Stauss HJ, et al. Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination. Blood 2011; 117:6813-24; PMID:21447831; http://dx.doi.org/10.1182/blood-2010-08-304568
101. Koesters R, Linnebacher M, Coy JF, Germann A, Schwitalle Y, Findeisen P, von Knebel Doeberitz M. WT1 is a tumor-associated antigen in colon cancer that can be recognized by in vitro stimulated cytotoxic T cells. Int J Cancer 2004; 109:385-92; PMID:14961577; http://dx.doi.org/10.1002/ ijc.11721
102. Inderberg-Suso EM, Trachsel S, Lislerud K, Rasmussen AM, Gaudernack G. Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. Oncoimmunology 2012; 1:670-86; PMID:22934259; http://dx.doi.org/10.4161/ onci.20426
103. Vermeij R, Leffers N, van der Burg SH, Melief CJ, Daemen T, Nijman HW. Immunological and clinical effects of vaccines targeting p53-overexpressing malignancies. J Biomed Biotechnol 2011; 2011:702146; PMID:21541192; http://dx.doi. org/10.1155/2011/702146
104. Galluzzi L, Morselli E, Kepp O, Tajeddine N, Kroemer G. Targeting p53 to mitochondria for cancer therapy. Cell Cycle 2008; 7:1949-55; PMID:18642442; http://dx.doi.org/10.4161/cc.7.13.6222
105. Umansky V, Malyguine A, Shurin M. New perspectives in cancer immunotherapy and immunomonitoring. Future Oncol 2009; 5:941-4; PMID:19792962; http://dx.doi.org/10.2217/fon.09.62
106. van der Burg SH. Therapeutic vaccines in cancer: moving from immunomonitoring to immunoguiding. Expert Rev Vaccines 2008; 7:1-5; PMID:18251686; http://dx.doi.org/10.1586/14760584.7.1.1
107. Hailemichael Y, Dai Z, Jaffarzad N, Ye Y, Medina MA, Huang XF, Dorta-Estremera SM, Greeley NR, Nitti G, Peng W, et al. Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion. Nat Med 2013; 19:465-72; PMID:23455713; http://dx.doi. org/10.1038/nm.3105
108. Ma Y, Xiang D, Sun J, Ding C, Liu M, Hu X, Li G, Kloecker G, Zhang HG, Yan J. Targeting of antigens to B lymphocytes via CD19 as a means for tumor vaccine development. J Immunol 2013; 190:5588-99; PMID:23630363; http://dx.doi.org/10.4049/ jimmunol.1203216
109. Sommerfeldt N, Beckhove P, Ge Y, Schütz F, Choi C, Bucur M, Domschke C, Sohn C, Schneeweis A, Rom J, et al. Heparanase: a new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes. Cancer Res 2006; 66:7716-23; PMID:16885374; http://dx.doi. org/10.1158/0008-5472.CAN-05-2363
110. Zhang J, Yang JM, Wang HJ, Ru GQ, Fan DM. Synthesized multiple antigenic polypeptide vaccine based on B-cell epitopes of human heparanase could elicit a potent antimetastatic effect on human hepatocellular carcinoma in vivo. PLoS One 2013; 8:e52940; PMID:23308126; http://dx.doi. org/10.1371/journal.pone.0052940
111. Dosset M, Vauchy C, Beziaud L, Adotevi O, Godet Y. Universal tumor-reactive helper peptides from telomerase as new tools for anticancer vaccination. Oncoimmunology 2013; 2:e23430; PMID:23802085; http://dx.doi.org/10.4161/ onci.23430
112. Dosset M, Godet Y, Vauchy C, Beziaud L, Lone YC, Sedlik C, Liard C, Levionnois E, Clerc B, Sandoval F, et al. Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor. Clin Cancer Res 2012; 18:6284-95; PMID:23032748; http://dx.doi. org/10.1158/1078-0432.CCR-12-0896
113. Brunsvig PF, Kyte JA, Kersten C, Sundstrøm S, Møller M, Nyakas M, Hansen GL, Gaudernack G, Aamdal S. Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin Cancer Res 2011; 17:6847-57; PMID:21918169; http://dx.doi.org/10.1158/1078-0432.CCR-11-1385
114. Kotsakis A, Vetsika EK, Christou S, Hatzidaki D, Vardakis N, Aggouraki D, Konsolakis G, Georgoulias V, Christophyllakis Ch, Cordopatis P, et al. Clinical outcome of patients with various advanced cancer types vaccinated with an optimized cryptic human telomerase reverse transcriptase (TERT) peptide: results of an expanded phase II study. Ann Oncol 2012; 23:442-9; PMID:21873272; http://dx.doi. org/10.1093/annonc/mdr396
115. Vetsika EK, Konsolakis G, Aggouraki D, Kotsakis A, Papadimitraki E, Christou S, Menez-Jamet J, Kosmatopoulos K, Georgoulias V, Mavroudis D. Immunological responses in cancer patients after vaccination with the therapeutic telomerase-specific vaccine Vx-001. Cancer Immunol Immunother 2012; 61:157-68; PMID:21858533; http://dx.doi. org/10.1007/s00262-011-1093-4
116. Hunger RE, Kernland Lang K, Markowski CJ, Trachsel S, Møller M, Eriksen JA, Rasmussen AM, Braathen LR, Gaudernack G. Vaccination of patients with cutaneous melanoma with telomerasespecific peptides. Cancer Immunol Immunother 2011; 60:1553-64; PMID:21681371; http://dx.doi. org/10.1007/s00262-011-1061-z
117. Kyte JA, Gaudernack G, Dueland S, Trachsel S, Julsrud L, Aamdal S. Telomerase peptide vaccination combined with temozolomide: a clinical trial in stage IV melanoma patients. Clin Cancer Res 2011; 17:4568-80; PMID:21586625; http://dx.doi. org/10.1158/1078-0432.CCR-11-0184
118. Schlapbach C, Yerly D, Daubner B, Yawalkar N, Hunger RE. Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma. J Dermatol Sci 2011; 62:75-83; PMID:21377838; http://dx.doi.org/10.1016/j.jdermsci.2011.02.001
119. Suso EM, Dueland S, Rasmussen AM, Vetrhus T, Aamdal S, Kvalheim G, Gaudernack G. hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes. Cancer Immunol Immunother 2011; 60:809-18; PMID:21365467; http://dx.doi.org/10.1007/s00262-011-0991-9
120. Rittig SM, Haentschel M, Weimer KJ, Heine A, Muller MR, Brugger W, Horger MS, Maksimovic O, Stenzl A, Hoerr I, et al. Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. Mol Ther 2011; 19:990-9; PMID:21189474; http://dx.doi.org/10.1038/ mt.2010.289
121. Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Fang HB, Cai L, Janofsky S, Chew A, Storek J, Akpek G, et al. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 2011; 117:788-97; PMID:21030558; http://dx.doi.org/10.1182/blood-2010-08-299396
122. Greten TF, Forner A, Korangy F, N'Kontchou G, Barget N, Ayuso C, Ormandy LA, Manns MP, Beaugrand M, Bruix J. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma. BMC Cancer 2010; 10:209; PMID:20478057; http://dx.doi. org/10.1186/1471-2407-10-209
123. Trepiakas R, Berntsen A, Hadrup SR, Bjørn J, Geertsen PF, Straten PT, Andersen MH, Pedersen AE, Soleimani A, Lorentzen T, et al. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial. Cytotherapy 2010; 12:721-34; PMID:20429791; http://dx.doi.org/10.3109/14653241003774045
124. Soleimani A, Berntsen A, Svane IM, Pedersen AE. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate. Scand J Immunol 2009; 70:481-9; PMID:19874553; http://dx.doi. org/10.1111/j.1365-3083.2009.02322.x
125. Aloysius MM, Mc Kechnie AJ, Robins RA, Verma C, Eremin JM, Farzaneh F, Habib NA, Bhalla J, Hardwick NR, Satthaporn S, et al. Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs. J Transl Med 2009; 7:18; PMID:19298672; http://dx.doi. org/10.1186/1479-5876-7-18
126. Berntsen A, Trepiakas R, Wenandy L, Geertsen PF, thor Straten P, Andersen MH, Pedersen AE, Claesson MH, Lorentzen T, Johansen JS, et al. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial. J Immunother 2008; 31:771-80; PMID:18779742; http://dx.doi.org/10.1097/CJI.0b013e3181833818
127. Bolonaki I, Kotsakis A, Papadimitraki E, Aggouraki D, Konsolakis G, Vagia A, Christophylakis C, Nikoloudi I, Magganas E, Galanis A, et al. Vaccination of patients with advanced non-smallcell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide. J Clin Oncol 2007; 25:2727-34; PMID:17602077; http://dx.doi. org/10.1200/JCO.2006.10.3465
128. Thorn M, Wang M, Kløverpris H, Schmidt EG, Fomsgaard A, Wenandy L, Berntsen A, Brunak S, Buus S, Claesson MH. Identification of a new hTERT-derived HLA-A*0201 restricted, naturally processed CTL epitope. Cancer Immunol Immunother 2007; 56:1755-63; PMID:17464507; http://dx.doi.org/10.1007/s00262-007-0319-y
129. Bernhardt SL, Gjertsen MK, Trachsel S, Møller M, Eriksen JA, Meo M, Buanes T, Gaudernack G. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study. Br J Cancer 2006; 95:1474-82; PMID:17060934; http://dx.doi.org/10.1038/ sj.bjc.6603437
130. Mavroudis D, Bolonakis I, Cornet S, Myllaki G, Kanellou P, Kotsakis A, Galanis A, Nikoloudi I, Spyropoulou M, Menez J, et al. A phase I study of the optimized cryptic peptide TERT(572y) in patients with advanced malignancies. Oncology 2006; 70:306-14; PMID:17047402; http://dx.doi. org/10.1159/000096252
131. Wierecky J, Müller MR, Wirths S, Halder-Oehler E, Dörfel D, Schmidt SM, Häntschel M, Brugger W, Schröder S, Horger MS, et al. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 2006; 66:5910-8; PMID:16740731; http://dx.doi.org/10.1158/0008-5472.CAN-05-3905
132. Brunsvig PF, Aamdal S, Gjertsen MK, Kvalheim G, Markowski-Grimsrud CJ, Sve I, Dyrhaug M, Trachsel S, Møller M, Eriksen JA, et al. Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother 2006; 55:1553-64; PMID:16491401; http://dx.doi.org/10.1007/s00262-006-0145-7
133. Märten A, Sievers E, Albers P, Müller S, Franchy C, von Ruecker A, Strunk H, Schild HH, Schmiedel A, Sommer T, et al. Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. Ger Med Sci 2006; 4:Doc02; PMID:19675693
134. Vonderheide RH, Domchek SM, Schultze JL, George DJ, Hoar KM, Chen DY, Stephans KF, Masutomi K, Loda M, Xia Z, et al. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 2004; 10:828-39; PMID:14871958; http://dx.doi. org/10.1158/1078-0432.CCR-0620-3
135. Middleton GW, Walle JW, Wadsley J, Propper D, Coxon FY, Ross PJ, et al. A phase III randomized trial of chemoimmunotherapy comprising gemcitabine and capecitabine with or without telomerase vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer. J Clin Oncol 2013; 31:abstr LBA4004
136. Kyte JA. Cancer vaccination with telomerase peptide GV1001. Expert Opin Investig Drugs 2009; 18:687-94; PMID:19388882; http://dx.doi. org/10.1517/13543780902897631
137. Kruit WH, Suciu S, Dreno B, Mortier L, Robert C, Chiarion-Sileni V, Maio M, Testori A, Dorval T, Grob JJ, et al. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma. J Clin Oncol 2013; 31:2413-20; PMID:23715572; http:// dx.doi.org/10.1200/JCO.2012.43.7111
138. Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, Spiessens B, Lehmann FF, Suciu S, Kruit WH, Eggermont AM, Vansteenkiste J, et al. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J Clin Oncol 2013; 31:2388-95; PMID:23715562; http://dx.doi.org/10.1200/ JCO.2012.44.3762
139. Burns WR, Zheng Z, Rosenberg SA, Morgan RA. Lack of specific gamma-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation. Blood 2009; 114:2888-99; PMID:19589923; http://dx.doi. org/10.1182/blood-2009-01-199216
140. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314:126-9; PMID:16946036; http://dx.doi.org/10.1126/ science.1129003
141. Hamilton E, Blackwell K, Hobeika AC, Clay TM, Broadwater G, Ren XR, Chen W, Castro H, Lehmann F, Spector N, et al. Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. [corrected]. J Transl Med 2012; 10:28; PMID:22325452; http:// dx.doi.org/10.1186/1479-5876-10-28
142. Andersen MH. The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase. Cancer Immunol Immunother 2012; 61:1289-97; PMID:22388712; http://dx.doi. org/10.1007/s00262-012-1234-4
143. Mavilio D, Galluzzi L, Lugli E. Novel multifunctional antibody approved for the treatment of breast cancer. Oncoimmunology 2013; 2:e24567; PMID:23802090; http://dx.doi.org/10.4161/ onci.24567
144. Kute T, Stehle JR Jr., Ornelles D, Walker N, Delbono O, Vaughn JP. Understanding key assay parameters that affect measurements of trastuzumab-mediated ADCC against Her2 positive breast cancer cells. Oncoimmunology 2012; 1:810-21; PMID:23162748; http://dx.doi.org/10.4161/onci.20447
145. Van Elssen CH, Frings PW, Bot FJ, Van de Vijver KK, Huls MB, Meek B, Hupperets P, Germeraad WT, Bos GM. Expression of aberrantly glycosylated Mucin-1 in ovarian cancer. Histopathology 2010; 57:597-606; PMID:20955385; http://dx.doi. org/10.1111/j.1365-2559.2010.03667.x
146. Lavrsen K, Madsen CB, Rasch MG, Woetmann A, Ødum N, Mandel U, Clausen H, Pedersen AE, Wandall HH. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity. Glycoconj J 2013; 30:227-36; PMID:22878593; http://dx.doi.org/10.1007/s10719-012-9437-7
147. Kroemer G, Zitvogel L, Galluzzi L. Victories and deceptions in tumor immunology: Stimuvax(®). Oncoimmunology 2013; 2:e23687; PMID:23483762; http://dx.doi.org/10.4161/ onci.23687
148. Schultz ES, Lethé B, Cambiaso CL, Van Snick J, Chaux P, Corthals J, Heirman C, Thielemans K, Boon T, van der Bruggen P. A MAGE-A3 peptide presented by HLA-DP4 is recognized on tumor cells by CD4+ cytolytic T lymphocytes. Cancer Res 2000; 60:6272-5; PMID:11103782
149. Trakatelli M, Toungouz M, Blocklet D, Dodoo Y, Gordower L, Laporte M, Vereecken P, Sales F, Mortier L, Mazouz N, et al. A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients. Cancer Immunol Immunother 2006; 55:469-74; PMID:16133111; http://dx.doi.org/10.1007/s00262-005-0056-z
150. Gahéry-Ségard H, Pialoux G, Figueiredo S, Igéa C, Surenaud M, Gaston J, Gras-Masse H, Lévy JP, Guillet JG. Long-term specific immune responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine: characterization of CD8+-T-cell epitopes recognized. J Virol 2003; 77:11220-31; PMID:14512570; http://dx.doi. org/10.1128/JVI.77.20.11220-11231.2003
151. Hackstein H, Knoche A, Nockher A, Poeling J, Kubin T, Jurk M, Vollmer J, Bein G. The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell differentiation via TLR8 and augments functional dendritic cell generation. Cell Immunol 2011; 271:401-12; PMID:21889130; http://dx.doi. org/10.1016/j.cellimm.2011.08.008
152. Igartua M, Pedraz JL. Topical resiquimod: a promising adjuvant for vaccine development? Expert Rev Vaccines 2010; 9:23-7; PMID:20021302; http:// dx.doi.org/10.1586/erv.09.135
153. Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R, Shir A, Herlyn M, Bar-Eli M, Levitzki A. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res 2013; 73:4383-94; PMID:23651636; http://dx.doi. org/10.1158/0008-5472.CAN-12-3385
154. Wilson AL, Schrecengost RS, Guerrero MS, Thomas KS, Bouton AH. Breast cancer antiestrogen resistance 3 (BCAR3) promotes cell motility by regulating actin cytoskeletal and adhesion remodeling in invasive breast cancer cells. PLoS One 2013; 8:e65678; PMID:23762409; http://dx.doi.org/10.1371/journal. pone.0065678
155. Mansfield AS, Nevala WK, Lieser EA, Leontovich AA, Markovic SN. The immunomodulatory effects of bevacizumab on systemic immunity in patients with metastatic melanoma. Oncoimmunology 2013; 2:e24436; PMID:23762809; http://dx.doi. org/10.4161/onci.24436
156. Michielsen AJ, Ryan EJ, O'Sullivan JN. Dendritic cell inhibition correlates with survival of colorectal cancer patients on bevacizumab treatment. Oncoimmunology 2012; 1:1445-7; PMID:23243624; http://dx.doi.org/10.4161/onci.21318
157. Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ, et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res 2005; 11:8055-62; PMID:16299236; http://dx.doi. org/10.1158/1078-0432.CCR-05-1203
158. Lin J, Lin L, Thomas DG, Greenson JK, Giordano TJ, Robinson GS, Barve RA, Weishaar FA, Taylor JM, Orringer MB, et al. Melanoma-associated antigens in esophageal adenocarcinoma: identification of novel MAGE-A10 splice variants. Clin Cancer Res 2004; 10:5708-16; PMID:15355897; http://dx.doi. org/10.1158/1078-0432.CCR-04-0468
159. Schultz-Thater E, Piscuoglio S, Iezzi G, Le Magnen C, Zajac P, Carafa V, Terracciano L, Tornillo L, Spagnoli GC. MAGE-A10 is a nuclear protein frequently expressed in high percentages of tumor cells in lung, skin and urothelial malignancies. Int J Cancer 2011; 129:1137-48; PMID:21710496; http:// dx.doi.org/10.1002/ijc.25777
160. Tsuji T, Matsuzaki J, Kelly MP, Ramakrishna V, Vitale L, He LZ, Keler T, Odunsi K, Old LJ, Ritter G, et al. Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity. J Immunol 2011; 186:1218-27; PMID:21149605; http://dx.doi.org/10.4049/jimmunol.1000808
161. Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G, Schuler-Thurner B, Schuler G, Schaft N, Dörrie J. Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation. Blood 2010; 116:2277-85; PMID:20566893; http://dx.doi.org/10.1182/ blood-2010-02-268425
162. Lainey E, Wolfromm A, Marie N, Enot D, Scoazec M, Bouteloup C, Leroy C, Micol JB, De Botton S, Galluzzi L, et al. Azacytidine and erlotinib exert synergistic effects against acute myeloid leukemia. Oncogene 2013; 32:4331-42; PMID:23085751; http://dx.doi.org/10.1038/onc.2012.469
163. Thépot S, Lainey E, Cluzeau T, Sébert M, Leroy C, Adès L, Tailler M, Galluzzi L, Baran-Marszak F, Roudot H, et al. Hypomethylating agents reactivate FOXO3A in acute myeloid leukemia. Cell Cycle 2011; 10:2323-30; PMID:21654193; http://dx.doi. org/10.4161/cc.10.14.16399
164. Weeratna RD, Makinen SR, McCluskie MJ, Davis HL. TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848). Vaccine 2005; 23:5263-70; PMID:16081189; http://dx.doi. org/10.1016/j.vaccine.2005.06.024
165. Hale DF, Clifton GT, Sears AK, Vreeland TJ, Shumway N, Peoples GE, Mittendorf EA. Cancer vaccines: should we be targeting patients with less aggressive disease? Expert Rev Vaccines 2012; 11:721-31; PMID:22873128; http://dx.doi.org/10.1586/ erv.12.39
166. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, et al. Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity. Clin Cancer Res 2008; 14:169-77; PMID:18172268; http://dx.doi.org/10.1158/1078-0432.CCR-07-1881
167. Levy A, Massard C, Gross-Goupil M, Fizazi K. Carcinomas of an unknown primary site: a curable disease? Ann Oncol 2008; 19:1657-8; PMID:18647966; http://dx.doi.org/10.1093/annonc/mdn430
168. Schuster SJ, Neelapu SS, Gause BL, Janik JE, Muggia FM, Gockerman JP, Winter JN, Flowers CR, Nikcevich DA, Sotomayor EM, et al. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol 2011; 29:2787-94; PMID:21632504; http://dx.doi.org/10.1200/ JCO.2010.33.3005
169. Kroemer G, Zitvogel L. Can the exome and the immunome converge on the design of efficient cancer vaccines? Oncoimmunology 2012; 1:579-80; PMID:22934249; http://dx.doi.org/10.4161/ onci.20730
170. Gilboa E. The makings of a tumor rejection antigen. Immunity 1999; 11:263-70; PMID:10514004; http://dx.doi.org/10.1016/S1074-7613(00)80101-6
171. Galluzzi L, Vacchelli E, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zucman-Rossi J, Zitvogel L, Kroemer G. Trial Watch: Monoclonal antibodies in cancer therapy. Oncoimmunology 2012; 1:28-37; PMID:22720209; http://dx.doi. org/10.4161/onci.1.1.17938
172. Vacchelli E, Eggermont A, Galon J, Sautès-Fridman C, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Monoclonal antibodies in cancer therapy. Oncoimmunology 2013; 2:e22789; PMID:23482847; http://dx.doi.org/10.4161/ onci.22789