Trial Watch: DNA vaccines for cancer therapy

OncoImmunology

Volumn 3, Issue 4, 2014, Pages 1-10

  Pol, Jonathan ^a,b,c,d   Bloy, Norma ^a,b,c,d   Obrist, Florine ^a,b,c,d   Eggermont, Alexander ^a   Galon, Jérôme ^c,e,f,g   Hervé Fridman, Wolf ^c,f,g   Cremer, Isabelle ^c,f,g   Zitvogel, Laurence ^a,g   Kroemer, Guido ^b,c,e,h,i   Galluzzi, Lorenzo ^a,c,e  

^a INSTITUT GUSTAVE ROUSSY   (France)

^b Institut Gustave Roussy   (France)

^c CENTRE DE RECHERCHE DES CORDELIERS   (France)

^d UNIVERSITÉ PARIS SACLAY   (France)

^e UNIVERSITÉ PARIS DESCARTES   (France)

^f SORBONNE UNIVERSITÉ   (France)

^g INSERM   (France)

^h HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

ⁱ Metabolomics Platform   (France)

Author keywords

Cross presentation; Dendritic cells; Electroporation; Listeria monocytogenes; Mucosal immunity; Saccharomyces cerevisiae

Indexed keywords

DNA VACCINE;

BLADDER CARCINOMA; BREAST CARCINOMA; BREAST METASTASIS; CANCER IMMUNIZATION; CANCER PREVENTION; CANCER STAGING; CANCER SURVIVAL; CLINICAL EFFECTIVENESS; COLORECTAL CARCINOMA; DIARRHEA; DNA IMMUNIZATION; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; ELECTROPORATION; FATIGUE; HUMAN; IMMUNOGENICITY; INJECTION SITE REACTION; NASOPHARYNX CANCER; NON MUSCLE INVASIVE BLADDER CANCER; NONHUMAN; OROPHARYNX CANCER; PROSTATE CANCER; REVIEW; SKIN MANIFESTATION; SOLID TUMOR; THYROID MEDULLARY CARCINOMA; TREATMENT DURATION; TREATMENT OUTCOME;

EID: 84902593489     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/onci.28185     Document Type: Review

References (170)

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. Finn OJ. Tumor immunology at the service of cancer immunotherapy. Curr Opin Immunol 2004; 16:127-9; PMID:15023402; http://dx.doi.org/10.1016/j. coi.2004.02.006
3. 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
4. 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
5. Vacchelli E, Vitale I, Eggermont A, Fridman WH, Fučíková J, Cremer I, Galon J, Tartour E, Zitvogel L, Kroemer G, et al. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology 2013; 2:e25771; PMID:24286020; http://dx.doi. org/10.4161/onci.25771
6. 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
7. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12:265-77; PMID:22437871; http://dx.doi.org/10.1038/ nrc3258
8. 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/ rc2373
9. Aranda F, Vacchelli E, Eggermont A, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Peptide vaccines in cancer therapy. Oncoimmunology 2013; 2:e26621; PMID:24498550; http://dx.doi.org/10.4161/onci.26621
10. 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
11. Rice J, Ottensmeier CH, Stevenson FK. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer 2008; 8:108-20; PMID:18219306; http://dx.doi. org/10.1038/nrc2326
12. Fioretti D, Iurescia S, Fazio VM, Rinaldi M. DNA vaccines: developing new strategies against cancer. J Biomed Biotechnol 2010; 2010:174378; PMID:20368780; http://dx.doi. org/10.1155/2010/174378
13. Liu MA. DNA vaccines: an historical perspective and view to the future. Immunol Rev 2011; 239:62-84; PMID:21198665; http://dx.doi. org/10.1111/j.1600-065X.2010.00980.x
14. Stevenson FK, Ottensmeier CH, Rice J. DNA vaccines against cancer come of age. Curr Opin Immunol 2010; 22:264-70; PMID:20172703; http://dx.doi.org/10.1016/j.coi.2010.01.019
15. Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ, Hong WK, Komaki R, Lee JJ, Nesbitt JC, et al. Retrovirus-mediated wildtype p53 gene transfer to tumors of patients with lung cancer. Nat Med 1996; 2:985-91; PMID:8782455; http://dx.doi.org/10.1038/nm0996-985
16. Maiuri MC, Galluzzi L, Morselli E, Kepp O, Malik SA, Kroemer G. AUtophagy Regulation By P53. Curr Opin Cell Biol 2010; 22:181-5; PMID:20044243; http://dx.doi.org/10.1016/j.ceb.2009.12.001
17. 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
18. INGN. INGN 201: Ad-p53, Ad5CMV-p53, adenoviral p53, p53 gene therapy--introgen, RPR/INGN 201. Drugs R D 2007; 8:176-87; PMID:17472413; http:// x.doi.org/10.2165/00126839-200708030-00005
19. Chawla SP, Chua VS, Fernandez L, Quon D, Saralou A, Blackwelder WC, Hall FL, Gordon EM. Phase I/II and phase II studies of targeted gene delivery in vivo:intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma. Mol Ther 2009; 17:1651-7; PMID:19532136; http://dx.doi.org/10.1038/mt.2009.126
20. Madhusudan S, Tamir A, Bates N, Flanagan E, Gore ME, Barton DP, Harper P, Seckl M, Thomas H, Lemoine NR, et al. A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene. Clin Cancer Res 2004; 10:2986-96; PMID:15131034; http://dx.doi.org/10.1158/1078-0432.CCR-03-0291
21. Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E, Reynolds TC, Murray JL. Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer. Clin Cancer Res 2001; 7:1237-45; PMID:11350889
22. Xing X, Liu V, Xia W, Stephens LC, Huang L, Lopez-Berestein G, Hung MC. Safety studies of the intraperitoneal injection of E1A--liposome complex in mice. Gene Ther 1997; 4:238-43; PMID:9135737; http://dx.doi.org/10.1038/sj.gt.3300376
23. Xing X, Zhang S, Chang JY, Tucker SD, Chen H, Huang L, Hung MC. Safety study and characterization of E1A-liposome complex genedelivery protocol in an ovarian cancer model. Gene Ther 1998; 5:1538-44; PMID:9930307; http://dx.doi.org/10.1038/sj.gt.3300771
24. Smaldone MC, Davies BJ. BC-819, a plasmid comprising the H19 gene regulatory sequences and diphtheria toxin A, for the potential targeted therapy of cancers. Curr Opin Mol Ther 2010; 12:607-16; PMID:20886393
25. Hanna N, Ohana P, Konikoff FM, Leichtmann G, Hubert A, Appelbaum L, Kopelman Y, Czerniak A, Hochberg A. Phase 1/2a, dose-escalation, safety, pharmacokinetic and preliminary efficacy study of intratumoral administration of BC-819 in patients with unresectable pancreatic cancer. Cancer Gene Ther 2012; 19:374-81; PMID:22498722; http://dx.doi.org/10.1038/cgt.2012.10
26. Trask TW, Trask RP, Aguilar-Cordova E, Shine HD, Wyde PR, Goodman JC, Hamilton WJ, Rojas-Martinez A, Chen SH, Woo SL, et al. Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 2000; 1:195-203; PMID:10933931; http://dx.doi.org/10.1006/mthe.2000.0030
27. Singh S, Cunningham C, Buchanan A, Jolly DJ, Nemunaitis J. Toxicity assessment of intratumoral injection of the herpes simplex type I thymidine kinase gene delivered by retrovirus in patients with refractory cancer. Mol Ther 2001; 4:157-60; PMID:11482988; http://dx.doi.org/10.1006/mthe.2001.0430
28. Germano IM, Fable J, Gultekin SH, Silvers A. Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. J Neurooncol 2003; 65:279-89; PMID:14682378; http://dx.doi. org/10.1023/B:NEON.0000003657.95085.56
29. Voges J, Reszka R, Gossmann A, Dittmar C, Richter R, Garlip G, Kracht L, Coenen HH, Sturm V, Wienhard K, et al. Imaging-guided convectionenhanced delivery and gene therapy of glioblastoma. Ann Neurol 2003; 54:479-87; PMID:14520660; http://dx.doi.org/10.1002/ana.10688
30. Kubo H, Gardner TA, Wada Y, Koeneman KS, Gotoh A, Yang L, Kao C, Lim SD, Amin MB, Yang H, et al. Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther 2003; 14:227-41; PMID:12639303; http://dx.doi.org/10.1089/10430340360535788
31. Nemunaitis J, Cunningham C, Senzer N, Kuhn J, Cramm J, Litz C, Cavagnolo R, Cahill A, Clairmont C, Sznol M. Pilot trial of genetically modified, attenuated Salmonella expressing the E. coli cytosine deaminase gene in refractory cancer patients. Cancer Gene Ther 2003; 10:737-44; PMID:14502226; http://dx.doi.org/10.1038/sj.cgt.7700634
32. Trudel S, Trachtenberg J, Toi A, Sweet J, Li ZH, Jewett M, Tshilias J, Zhuang LH, Hitt M, Wan Y, et al. A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer. Cancer Gene Ther 2003; 10:755-63; PMID:14502228; http://dx.doi.org/10.1038/ j.cgt.7700626
33. Galanis E, Hersh EM, Stopeck AT, Gonzalez R, Burch P, Spier C, Akporiaye ET, Rinehart JJ, Edmonson J, Sobol RE, et al. Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex:phase I/II experience. J Clin Oncol 1999; 17:3313-23; PMID:10506635
34. Belldegrun A, Tso CL, Zisman A, Naitoh J, Said J, Pantuck AJ, Hinkel A, deKernion J, Figlin R. Interleukin 2 gene therapy for prostate cancer: phase I clinical trial and basic biology. Hum Gene Ther 2001; 12:883-92; PMID:11387054; http://dx.doi. org/10.1089/104303401750195854
35. Horton HM, Lalor PA, Rolland AP. IL-2 plasmid electroporation: from preclinical studies to phase I clinical trial. Methods Mol Biol 2008; 423:361-72; PMID:18370214; http://dx.doi. org/10.1007/978-1-59745-194-9_28
36. Heinzerling L, Burg G, Dummer R, Maier T, Oberholzer PA, Schultz J, Elzaouk L, Pavlovic J, Moelling K. Intratumoral injection of DNA encoding human interleukin 12 into patients with metastatic melanoma: clinical efficacy. Hum Gene Ther 2005; 16:35-48; PMID:15703487; http://dx.doi. org/10.1089/hum.2005.16.35
37. Mahvi DM, Henry MB, Albertini MR, Weber S, Meredith K, Schalch H, Rakhmilevich A, Hank J, Sondel P. Intratumoral injection of IL-12 plasmid DNA--results of a phase I/IB clinical trial. Cancer Gene Ther 2007; 14:717-23; PMID:17557109; http://dx.doi.org/10.1038/sj.cgt.7701064
38. Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, et al. Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 2008; 26:5896-903; PMID:19029422
39. Anwer K, Barnes MN, Fewell J, Lewis DH, Alvarez RD. Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer. Gene Ther 2010; 17:360-9; PMID:20033066; http://dx.doi.org/10.1038/gt.2009.159
40. Hernandez-Alcoceba R, Berraondo P. Immunochemotherapy against colon cancer by gene transfer of interleukin-12 in combination with oxaliplatin. Oncoimmunology 2012; 1:97-9; PMID:22720223; http://dx.doi.org/10.4161/ nci.1.1.17930
41. Khorana AA, Rosenblatt JD, Sahasrabudhe DM, Evans T, Ladrigan M, Marquis D, Rosell K, Whiteside T, Phillippe S, Acres B, et al. A phase I trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma. Cancer Gene Ther 2003; 10:251-9; PMID:12679797; http://dx.doi. org/10.1038/sj.cgt.7700568
42. Dummer R, Hassel JC, Fellenberg F, Eichmüller S, Maier T, Slos P, Acres B, Bleuzen P, Bataille V, Squiban P, et al. Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood 2004; 104:1631-8; PMID:15161670; http://dx.doi. org/10.1182/blood-2004-01-0360
43. Nemunaitis J, Fong T, Robbins JM, Edelman G, Edwards W, Paulson RS, Bruce J, Ognoskie N, Wynne D, Pike M, et al. Phase I trial of interferongamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma. Cancer Gene Ther 1999; 6:322-30; PMID:10419050; http://dx.doi.org/10.1038/sj.cgt.7700019
44. Merrick AE, Ilett EJ, Melcher AA. JX-594, a targeted oncolytic poxvirus for the treatment of cancer. Curr Opin Investig Drugs 2009; 10:1372-82; PMID:19943208
45. Malmström PU, Loskog AS, Lindqvist CA, Mangsbo SM, Fransson M, Wanders A, Gårdmark T, Tötterman TH. AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial. Clin Cancer Res 2010; 16:3279-87; PMID:20448220; http://dx.doi.org/10.1158/1078-0432.CCR-10-0385
46. Castro JE, Melo-Cardenas J, Urquiza M, Barajas-Gamboa JS, Pakbaz RS, Kipps TJ. Gene immunotherapy of chronic lymphocytic leukemia:a phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule. Cancer Res 2012; 72:2937-48; PMID:22505652; http://dx.doi. org/10.1158/0008-5472.CAN-11-3368
47. Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci U S A 1993; 90:11307-11; PMID:8248244; http://dx.doi. org/10.1073/pnas.90.23.11307
48. Nabel GJ, Gordon D, Bishop DK, Nickoloff BJ, Yang ZY, Aruga A, Cameron MJ, Nabel EG, Chang AE. Immune response in human melanoma after transfer of an allogeneic class I major histocompatibility complex gene with DNA-liposome complexes. Proc Natl Acad Sci U S A 1996; 93:15388-93; PMID:8986821; http://dx.doi.org/10.1073/pnas.93.26.15388
49. Rubin J, Galanis E, Pitot HC, Richardson RL, Burch PA, Charboneau JW, Reading CC, Lewis BD, Stahl S, Akporiaye ET, et al. Phase I study of immunotherapy of hepatic metastases of colorectal carcinoma by direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7. Gene Ther 1997; 4:419-25; PMID:9274718; http://dx.doi. org/10.1038/sj.gt.3300396
50. Stopeck AT, Hersh EM, Akporiaye ET, Harris DT, Grogan T, Unger E, Warneke J, Schluter SF, Stahl S. Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma. J Clin Oncol 1997; 15:341-9; PMID:8996161
51. Gleich LL, Gluckman JL, Armstrong S, Biddinger PW, Miller MA, Balakrishnan K, Wilson KM, Saavedra HI, Stambrook PJ. Alloantigen gene therapy for squamous cell carcinoma of the head and neck:results of a phase-1 trial. Arch Otolaryngol Head Neck Surg 1998; 124:1097-104; PMID:9776187; http://dx.doi.org/10.1001/archotol.124.10.1097
52. Rini BI, Selk LM, Vogelzang NJ. Phase I study of direct intralesional gene transfer of HLA-B7 into metastatic renal carcinoma lesions. Clin Cancer Res 1999; 5:2766-72; PMID:10537340
53. Stopeck AT, Jones A, Hersh EM, Thompson JA, Finucane DM, Gutheil JC, Gonzalez R. Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin Cancer Res 2001; 7:2285-91; PMID:11489803
54. Gonzalez R, Hutchins L, Nemunaitis J, Atkins M, Schwarzenberger PO. Phase 2 trial of Allovectin-7 in advanced metastatic melanoma. Melanoma Res 2006; 16:521-6; PMID:17119453; http://dx.doi. org/10.1097/01.cmr.0000232299.44902.41
55. Bedikian AY, Richards J, Kharkevitch D, Atkins MB, Whitman E, Gonzalez R. A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. Melanoma Res 2010; 20:218-26; PMID:20354459
56. 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
57. Haniffa M, Collin M, Ginhoux F. Identification of human tissue cross-presenting dendritic cells: A new target for cancer vaccines. Oncoimmunology 2013; 2:e23140; PMID:23802067; http://dx.doi. org/10.4161/onci.23140
58. Larocca C, Schlom J. Viral vector-based therapeutic cancer vaccines. Cancer J 2011; 17:359-71; PMID:21952287; http://dx.doi.org/10.1097/ PO.0b013e3182325e63
59. Cawood R, Hills T, Wong SL, Alamoudi AA, Beadle S, Fisher KD, Seymour LW. Recombinant viral vaccines for cancer. Trends Mol Med 2012; 18:564-74; PMID:22917663; http://dx.doi.org/10.1016/j. molmed.2012.07.007
60. Bridle BW, Clouthier D, Zhang L, Pol J, Chen L, Lichty BD, Bramson JL, Wan Y. Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves primary CD8(+) T-cell responses to anticancer vaccines. Oncoimmunology 2013; 2:e26013; PMID:24083086; http://dx.doi. org/10.4161/onci.26013
61. Zhou Q, Buchholz CJ. Cell type specific gene delivery by lentiviral vectors: New options in immunotherapy. Oncoimmunology 2013; 2:e22566; PMID:23483777; http://dx.doi.org/10.4161/onci.22566
62. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, Lim A, Osborne CS, Pawliuk R, Morillon E, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302:415-9; PMID:14564000; http://dx.doi. org/10.1126/science.1088547
63. 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
64. 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
65. 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
66. Lu S, Wang S, Grimes-Serrano JM. Current progress of DNA vaccine studies in humans. Expert Rev Vaccines 2008; 7:175-91; PMID:18324888; http:// x.doi.org/10.1586/14760584.7.2.175
67. Nardelli-Haefliger D, Romero P, Jichlinski P. What is the influence of vaccination's routes on the regression of tumors located at mucosal sites? Oncoimmunology 2012; 1:242-3; PMID:22720257; http://dx.doi. org/10.4161/onci.1.2.18204
68. Dupuis M, Denis-Mize K, Woo C, Goldbeck C, Selby MJ, Chen M, Otten GR, Ulmer JB, Donnelly JJ, Ott G, et al. Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice. J Immunol 2000; 165:2850-8; PMID:10946318
69. Best SR, Peng S, Juang CM, Hung CF, Hannaman D, Saunders JR, Wu TC, Pai SI. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery. Vaccine 2009; 27:5450-9; PMID:19622402; http://dx.doi.org/10.1016/j.vaccine.2009.07.005
70. Fuller DH, Loudon P, Schmaljohn C. Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases. Methods 2006; 40:86-97; PMID:16997717; http://dx.doi.org/10.1016/j. ymeth.2006.05.022
71. Hallermalm K, Johansson S, Bråve A, Ek M, Engström G, Boberg A, Gudmundsdotter L, Blomberg P, Mellstedt H, Stout R, et al. Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer. Scand J Immunol 2007; 66:43-51; PMID:17587345; http://dx.doi.org/10.1111/j.1365-3083.2007.01945.x
72. Nguyen-Hoai T, Kobelt D, Hohn O, Vu MD, Schlag PM, Dörken B, Norley S, Lipp M, Walther W, Pezzutto A, et al. HER2/neu DNA vaccination by intradermal gene delivery in a mouse tumor model: Gene gun is superior to jet injector in inducing CTL responses and protective immunity. Oncoimmunology 2012; 1:1537-45; PMID:23264900; http://dx.doi. org/10.4161/onci.22563
73. van den Berg JH, Nujien B, Beijnen JH, Vincent A, van Tinteren H, Kluge J, Woerdeman LA, Hennink WE, Storm G, Schumacher TN, et al. Optimization of intradermal vaccination by DNA tattooing in human skin. Hum Gene Ther 2009; 20:181-9; PMID:19301471; http://dx.doi.org/10.1089/ um.2008.073
74. Fest S, Huebener N, Bleeke M, Durmus T, Stermann A, Woehler A, Baykan B, Zenclussen AC, Michalsky E, Jaeger IS, et al. Survivin minigene DNA vaccination is effective against neuroblastoma. Int J Cancer 2009; 125:104-14; PMID:19291796; http://dx.doi.org/10.1002/ijc.24291
75. Niethammer AG, Lubenau H, Mikus G, Knebel P, Hohmann N, Leowardi C, Beckhove P, Akhisaroglu M, Ge Y, Springer M, et al. Double-blind, placebocontrolled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer. BMC Cancer 2012; 12:361; PMID:22906006; http://dx.doi. org/10.1186/1471-2407-12-361
76. Meng JZ, Dong YJ, Huang H, Li S, Zhong Y, Liu SL, Wang YD. Oral vaccination with attenuated Salmonella enterica strains encoding T-cell epitopes from tumor antigen NY-ESO-1 induces specific cytotoxic T-lymphocyte responses. Clin Vaccine Immunol 2010; 17:889-94; PMID:20375244; http://dx.doi.org/10.1128/CVI.00044-10
77. Liu J, Kjeken R, Mathiesen I, Barouch DH. Recruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation. J Virol 2008; 82:5643-9; PMID:18353952; http://dx.doi. org/10.1128/JVI.02564-07
78. Ahlén G, Söderholm J, Tjelle T, Kjeken R, Frelin L, Höglund U, Blomberg P, Fons M, Mathiesen I, Sällberg M. In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells. J Immunol 2007; 179:4741-53; PMID:17878373
79. Buchan S, Grønevik E, Mathiesen I, King CA, Stevenson FK, Rice J. Electroporation as a "prime/boost" strategy for naked DNA vaccination against a tumor antigen. J Immunol 2005; 174:6292-8; PMID:15879128
80. Aihara H, Miyazaki J. Gene transfer into muscle by electroporation in vivo. Nat Biotechnol 1998; 16:867-70; PMID:9743122; http://dx.doi.org/10.1038/nbt0998-867
81. Mathiesen I. Electropermeabilization of skeletal muscle enhances gene transfer in vivo. Gene Ther 1999; 6:508-14; PMID:10476210; http://dx.doi. org/10.1038/sj.gt.3300847
82. Mir LM, Bureau MF, Gehl J, Rangara R, Rouy D, Caillaud JM, Delaere P, Branellec D, Schwartz B, Scherman D. High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc Natl Acad Sci U S A 1999; 96:4262-7; PMID:10200250; http://dx.doi.org/10.1073/pnas.96.8.4262
83. Murakami T, Sunada Y. Plasmid DNA gene therapy by electroporation: principles and recent advances. Curr Gene Ther 2011; 11:447-56; PMID:22023474; http://dx.doi.org/10.2174/156652311798192860
84. Galluzzi L, Kepp O, Kroemer G. Immunogenic cell death in radiation therapy. Oncoimmunology 2013; 2:e26536; PMID:24404424; http://dx.doi. org/10.4161/onci.26536
85. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31:51-72; PMID:23157435; http://dx.doi.org/10.1146/annurev-immunol-032712-100008
86. Galluzzi L, Kepp O, Kroemer G. Mitochondria:master regulators of danger signalling. Nat Rev Mol Cell Biol 2012; 13:780-8; PMID:23175281; http://dx.doi.org/10.1038/nrm3479
87. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 2005; 5:615-25; PMID:16034368; http://dx.doi.org/10.1038/nrc1669
88. Suri A, Saini S, Sinha A, Agarwal S, Verma A, Parashar D, Singh S, Gupta N, Jagadish N. Cancer testis antigens: A new paradigm for cancer therapy. Oncoimmunology 2012; 1:1194-6; PMID:23170277; http://dx.doi.org/10.4161/onci.20686
89. Davis BS, Chang GJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML. West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. J Virol 2001; 75:4040-7; PMID:11287553; http://dx.doi. org/10.1128/JVI.75.9.4040-4047.2001
90. Anderson ED, Mourich DV, Leong JA. Gene expression in rainbow trout (Oncorhynchus mykiss) following intramuscular injection of DNA. Mol Mar Biol Biotechnol 1996; 5:105-13; PMID:8680523
91. Anderson ED, Mourich DV, Fahrenkrug SC, LaPatra S, Shepherd J, Leong JA. Genetic immunization of rainbow trout (Oncorhynchus mykiss) against infectious hematopoietic necrosis virus. Mol Mar Biol Biotechnol 1996; 5:114-22; PMID:8680524
92. 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
93. Diaz CM, Chiappori A, Aurisicchio L, Bagchi A, Clark J, Dubey S, Fridman A, Fabregas JC, Marshall J, Scarselli E, et al. Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors. J Transl Med 2013; 11:62; PMID:23497415; http://dx.doi. org/10.1186/1479-5876-11-62
94. Eriksson F, Tötterman T, Maltais AK, Pisa P, Yachnin J. DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer. Vaccine 2013; 31:3843-8; PMID:23831327; http://dx.doi. org/10.1016/j.vaccine.2013.06.063
95. Tiriveedhi V, Fleming TP, Goedegebuure PS, Naughton M, Ma C, Lockhart C, Gao F, Gillanders WE, Mohanakumar T. Mammaglobin-A cDNA vaccination of breast cancer patients induces antigenspecific cytotoxic CD4+ICOShi T cells. Breast Cancer Res Treat 2013; 138:109-18; PMID:22678162; http://dx.doi.org/10.1007/s10549-012-2110-9
96. Bilusic M, Heery CR, Arlen PM, Rauckhorst M, Apelian D, Tsang KY, Tucker JA, Jochems C, Schlom J, Gulley JL, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother 2014; 63:225-34; PMID:24327292; http://dx.doi.org/10.1007/s00262-013-1505-8
97. Hui EP, Taylor GS, Jia H, Ma BB, Chan SL, Ho R, Wong WL, Wilson S, Johnson BF, Edwards C, et al. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res 2013; 73:1676-88; PMID:23348421; http://dx.doi. org/10.1158/0008-5472.CAN-12-2448
98. Slovin SF, Kehoe M, Durso R, Fernandez C, Olson W, Gao JP, Israel R, Scher HI, Morris S. A phase I dose escalation trial of vaccine replicon particles (VRP) expressing prostate-specific membrane antigen (PSMA) in subjects with prostate cancer. Vaccine 2013; 31:943-9; PMID:23246260; http:// x.doi.org/10.1016/j.vaccine.2012.11.096
99. Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991; 324:1156-61; PMID:1707140; http://dx.doi. org/10.1056/NEJM199104253241702
100. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987; 317:909-16; PMID:2442609; http:// x.doi.org/10.1056/NEJM198710083171501
101. Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 2013; 368:1314-25; PMID:23550669; http://dx.doi.org/10.1056/NEJMoa1212299
102. Sartor O. Androgen deprivation--continuous, intermittent, or none at all? N Engl J Med 2012; 367:945-6; PMID:22931264; http://dx.doi. org/10.1056/NEJMe1206814
103. Tang S, Dubey P. Opposing effects of androgen ablation on immune function in prostate cancer. Oncoimmunology 2012; 1:1220-1; PMID:23170287; http://dx.doi.org/10.4161/onci.20448
104. Schmidt HH, Ge Y, Hartmann FJ, Conrad H, Klug F, Nittel S, Bernhard H, Domschke C, Schuetz F, Sohn C, et al. HLA Class II tetramers reveal tissue-specific regulatory T cells that suppress T-cell responses in breast carcinoma patients. Oncoimmunology 2013; 2:e24962; PMID:23894725; http://dx.doi. org/10.4161/onci.24962
105. Watson MA, Dintzis S, Darrow CM, Voss LE, DiPersio J, Jensen R, Fleming TP. Mammaglobin expression in primary, metastatic, and occult breast cancer. Cancer Res 1999; 59:3028-31; PMID:10397237
106. Zehentner BK, Carter D. Mammaglobin: a candidate diagnostic marker for breast cancer. Clin Biochem 2004; 37:249-57; PMID:15003725; http://dx.doi. org/10.1016/j.clinbiochem.2003.11.005
107. Faget J, Sisirak V, Blay JY, Caux C, Bendriss-Vermare N, Ménétrier-Caux C. ICOS is associated with poor prognosis in breast cancer as it promotes the amplification of immunosuppressive CD4(+) T cells by plasmacytoid dendritic cells. Oncoimmunology 2013; 2:e23185; PMID:23802069; http://dx.doi. org/10.4161/onci.23185
108. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012; 30:531-64; PMID:22224781; http://dx.doi.org/10.1146/annurev.immunol.25.022106.141623
109. von Boehmer H, Daniel C. Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer. Nat Rev Drug Discov 2013; 12:51-63; PMID:23274471; http://dx.doi.org/10.1038/nrd3683
110. Blatner NR, Gounari F, Khazaie K. The two faces of regulatory T cells in cancer. Oncoimmunology 2013; 2:e23852; PMID:23762787; http://dx.doi. org/10.4161/onci.23852
111. Wang D, Rayani S, Marshall JL. Carcinoembryonic antigen as a vaccine target. Expert Rev Vaccines 2008; 7:987-93; PMID:18767948; http://dx.doi. org/10.1586/14760584.7.7.987
112. Sarobe P, Huarte E, Lasarte JJ, Borrás-Cuesta F. Carcinoembryonic antigen as a target to induce antitumor immune responses. Curr Cancer Drug Targets 2004; 4:443-54; PMID:15320719; http://dx.doi. org/10.2174/1568009043332916
113. Kass ES, Greiner JW, Kantor JA, Tsang KY, Guadagni F, Chen Z, Clark B, De Pascalis R, Schlom J, Van Waes C. Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer. Cancer Res 2002; 62:5049-57; PMID:12208760
114. Stern HM. Improving treatment of HER2-positive cancers: opportunities and challenges. Sci Transl Med 2012; 4:127rv2; PMID:22461643; http:// x.doi.org/10.1126/scitranslmed.3001539
115. Hurvitz SA, Hu Y, O'Brien N, Finn RS. Current approaches and future directions in the treatment of HER2-positive breast cancer. Cancer Treat Rev 2013; 39:219-29; PMID:22658319; http://dx.doi. org/10.1016/j.ctrv.2012.04.008
116. Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 2011; 9:16-32; PMID:22124364; http://dx.doi.org/10.1038/nrclinonc.2011.177
117. Facciabene A, Aurisicchio L, Elia L, Palombo F, Mennuni C, Ciliberto G, La Monica N. Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile enterotoxin elicit antigenspecific immune responses and antitumor effects. Vaccine 2007; 26:47-58; PMID:18055074; http:// x.doi.org/10.1016/j.vaccine.2007.10.060
118. Weltzin R, Guy B, Thomas WD Jr., Giannasca PJ, Monath TP. Parenteral adjuvant activities of Escherichia coli heat-labile toxin and its B subunit for immunization of mice against gastric Helicobacter pylori infection. Infect Immun 2000; 68:2775-82; PMID:10768972; http://dx.doi.org/10.1128/ AI.68.5.2775-2782.2000
119. Hyslop T, Waldman SA. Guanylyl cyclase C as a biomarker in colorectal cancer. Biomark Med 2013; 7:159-67; PMID:23387497; http://dx.doi. org/10.2217/bmm.12.90
120. Carrithers SL, Barber MT, Biswas S, Parkinson SJ, Park PK, Goldstein SD, Waldman SA. Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues. Proc Natl Acad Sci U S A 1996; 93:14827-32; PMID:8962140; http://dx.doi.org/10.1073/pnas.93.25.14827
121. Alexander J, del Guercio MF, Maewal A, Qiao L, Fikes J, Chesnut RW, Paulson J, Bundle DR, DeFrees S, Sette A. Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses. J Immunol 2000; 164:1625-33; PMID:10640784
122. Rosa DS, Tzelepis F, Cunha MG, Soares IS, Rodrigues MM. The pan HLA DR-binding epitope improves adjuvant-assisted immunization with a recombinant protein containing a malaria vaccine candidate. Immunol Lett 2004; 92:259-68; PMID:15081621; http://dx.doi.org/10.1016/j.imlet.2004.01.006
123. Gilbert SC. Clinical development of Modified Vaccinia virus Ankara vaccines. Vaccine 2013; 31:4241-6; PMID:23523410; http://dx.doi. org/10.1016/j.vaccine.2013.03.020
124. Acres B, Bonnefoy JY. Clinical development of MVA-based therapeutic cancer vaccines. Expert Rev Vaccines 2008; 7:889-93; PMID:18767940; http:// x.doi.org/10.1586/14760584.7.7.889
125. Klein E, Nagy N, Rasul AE. EBV genome carrying B lymphocytes that express the nuclear protein EBNA-2 but not LMP-1: Type IIb latency. Oncoimmunology 2013; 2:e23035; PMID:23526738; http://dx.doi. org/10.4161/onci.23035
126. Smith C, Khanna R. A new approach for cellular immunotherapy of nasopharyngeal carcinoma. Oncoimmunology 2012; 1:1440-2; PMID:23243622; http://dx.doi.org/10.4161/onci.21286
127. Payton S. Prostate cancer: MDV3100 has antitumor activity in castration-resistant disease. Nat Rev Urol 2010; 7:300; PMID:20545033; http://dx.doi. org/10.1038/nrurol.2010.69
128. Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, et al.; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castrationresistant prostate cancer: a phase 1-2 study. Lancet 2010; 375:1437-46; PMID:20398925; http://dx.doi. org/10.1016/S0140-6736(10)60172-9
129. Tsao CK, Oh WK. Urological cancer: Enzalutamide in metastatic CRPC-old dog, new tricks. Nat Rev Clin Oncol 2012; 9:613-4; PMID:23044775; http:// .doi.org/10.1038/nrclinonc.2012.181
130. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, et al.; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367:1187-97; PMID:22894553; http://dx.doi.org/10.1056/NEJMoa1207506
131. Doehn C, Kausch I, Böhmer T, Sommerauer M, Jocham D. Drug evaluation: Therion's rV-PSATRICOM + rF-PSA-TRICOM prime-boost prostate cancer vaccine. Curr Opin Mol Ther 2007; 9:183-9; PMID:17458173
132. DiPaola RS, Plante M, Kaufman H, Petrylak DP, Israeli R, Lattime E, Manson K, Schuetz T. A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer. J Transl Med 2006; 4:1; PMID:16390546; http://dx.doi. org/10.1186/1479-5876-4-1
133. Geary SM, Salem AK. Prostate cancer vaccines:Update on clinical development. Oncoimmunology 2013; 2:e24523; PMID:23762812; http://dx.doi. org/10.4161/onci.24523
134. Gerritsen WR. The evolving role of immunotherapy in prostate cancer. Ann Oncol 2012; 23(Suppl 8):viii22-7; PMID:22918924; http://dx.doi. org/10.1093/annonc/mds259
135. Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin Oncol 2012; 39:296-304; PMID:22595052; http://dx.doi.org/10.1053/j. seminoncol.2012.02.010
136. Brockhausen I. Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep 2006; 7:599-604; PMID:16741504; http://dx.doi.org/10.1038/sj.embor.7400705
137. Devine PL, McKenzie IF. Mucins: structure, function, and associations with malignancy. Bioessays 1992; 14:619-25; PMID:1365918; http://dx.doi. org/10.1002/bies.950140909
138. Reichenbach DK, Finn OJ. Early in vivo signaling profiles in MUC1-specific CD4(+) T cells responding to two different MUC1-targeting vaccines in two different microenvironments. Oncoimmunology 2013; 2:e23429; PMID:23802084; http://dx.doi. org/10.4161/onci.23429
139. Avogadri F, Merghoub T, Maughan MF, Hirschhorn-Cymerman D, Morris J, Ritter E, Olmsted R, Houghton AN, Wolchok JD. Alphavirus replicon particles expressing TRP-2 provide potent therapeutic effect on melanoma through activation of humoral and cellular immunity. PLoS One 2010; 5:e12670; PMID:20844763; http://dx.doi.org/10.1371/ journal.pone.0012670
140. Morse MA, Hobeika AC, Osada T, Berglund P, Hubby B, Negri S, Niedzwiecki D, Devi GR, Burnett BK, Clay TM, et al. An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer. J Clin Invest 2010; 120:3234-41; PMID:20679728; http://dx.doi. org/10.1172/JCI42672
141. Atkins GJ, Fleeton MN, Sheahan BJ. Therapeutic and prophylactic applications of alphavirus vectors. Expert Rev Mol Med 2008; 10:e33; PMID:19000329; http://dx.doi.org/10.1017/S1462399408000859
142. Elsässer-Beile U, Bühler P, Wolf P. Targeted therapies for prostate cancer against the prostate specific membrane antigen. Curr Drug Targets 2009; 10:118-25; PMID:19199907; http://dx.doi. org/10.2174/138945009787354601
143. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol 2004; 6(Suppl 10):S13-8; PMID:16985927
144. Galluzzi L. New immunotherapeutic paradigms for castration-resistant prostate cancer. OncoImmunology 2013; 2:e26084; http://dx.doi. org/10.4161/onci.26084
145. Remondo C, Cereda V, Mostböck S, Sabzevari H, Franzusoff A, Schlom J, Tsang KY. Human dendritic cell maturation and activation by a heatkilled recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen. Vaccine 2009; 27:987-94; PMID:19110021; http://dx.doi. org/10.1016/j.vaccine.2008.12.002
146. Wansley EK, Chakraborty M, Hance KW, Bernstein MB, Boehm AL, Guo Z, Quick D, Franzusoff A, Greiner JW, Schlom J, et al. Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses. Clin Cancer Res 2008; 14:4316-25; PMID:18594015; http://dx.doi. org/10.1158/1078-0432.CCR-08-0393
147. Isaacson P, Judd MA. Carcinoembryonic antigen in medullary carcinoma of thyroid. Lancet 1976; 2:1016-7; PMID:62227; http://dx.doi.org/10.1016/ S0140-6736(76)90847-3
148. Ishikawa N, Hamada S. Association of medullary carcinoma of the thyroid with carcinoembryonic antigen. Br J Cancer 1976; 34:111-5; PMID:962990; http://dx.doi.org/10.1038/bjc.1976.133
149. Meyer JS, Abdel-Bari W. Granules and thyrocalcitonin-like activity in medullary carcinoma of the thyroid gland. N Engl J Med 1968; 278:523-9; PMID:5637238; http://dx.doi.org/10.1056/ NEJM196803072781002
150. Melvin KE, Tashjian AH Jr. The syndrome of excessive thyrocalcitonin produced by medullary carcinoma of the thyroid. Proc Natl Acad Sci U S A 1968; 59:1216-22; PMID:5240025; http://dx.doi. org/10.1073/pnas.59.4.1216
151. Tashjian AH Jr., Melvin EW. Medullary carcinoma of the thyroid gland. Studies of thyrocalcitonin in plasma and tumor extracts. N Engl J Med 1968; 279:279-83; PMID:5660301; http://dx.doi. org/10.1056/NEJM196808082790602
152. Guirnalda P, Wood L, Goenka R, Crespo J, Paterson Y. Interferon γ-induced intratumoral expression of CXCL9 alters the local distribution of T cells following immunotherapy with Listeria monocytogenes. Oncoimmunology 2013; 2:e25752; PMID:24083082; http://dx.doi.org/10.4161/ onci.25752
153. Rothman J, Paterson Y. Live-attenuated Listeriabased immunotherapy. Expert Rev Vaccines 2013; 12:493-504; PMID:23659298; http://dx.doi. org/10.1586/erv.13.34
154. Guirnalda PD, Paterson Y. Vaccination with immunotherapeutic Listeria monocytogenes induces IL-17(+) γδ T cells in a murine model for HPV associated cancer. Oncoimmunology 2012; 1:822-8; PMID:23162749; http://dx.doi.org/10.4161/ onci.20491
155. Mustafa W, Maciag PC, Pan ZK, Weaver JR, Xiao Y, Isaacs SN, Paterson Y. Listeria monocytogenes delivery of HPV-16 major capsid protein L1 induces systemic and mucosal cell-mediated CD4+ and CD8+ T-cell responses after oral immunization. Viral Immunol 2009; 22:195-204; PMID:19435416; http://dx.doi.org/10.1089/vim.2008.0071
156. Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnù L, et al. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 2006; 101:524-32; PMID:16542289; http://dx.doi. org/10.1111/j.1572-0241.2006.00443.x
157. Morse MA, Chaudhry A, Gabitzsch ES, Hobeika AC, Osada T, Clay TM, Amalfitano A, Burnett BK, Devi GR, Hsu DS, et al. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother 2013; 62:1293-301; PMID:23624851; http://dx.doi.org/10.1007/ s00262-013-1400-3
158. Gavazza A, Lubas G, Fridman A, Peruzzi D, Impellizeri JA, Luberto L, Marra E, Roscilli G, Ciliberto G, Aurisicchio L. Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell lymphoma. Hum Gene Ther 2013; 24:728-38; PMID:23902422; http://dx.doi. org/10.1089/hum.2013.112
159. 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
160. 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
161. 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
162. 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
163. Vitale I, Galluzzi L, Castedo M, Kroemer G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol 2011; 12:385-92; PMID:21527953; http://dx.doi.org/10.1038/ nrm3115
164. Hsu A, Ritchie DS, Neeson P. Are the immunostimulatory properties of Lenalidomide extinguished by co-administration of Dexamethasone? Oncoimmunology 2012; 1:372-4; PMID:22737619; http://dx.doi.org/10.4161/onci.18963
165. Nasir L. Telomeres and telomerase: Biological and clinical importance in dogs. Vet J 2008; 175:155-63; PMID:17398127; http://dx.doi.org/10.1016/j. tvjl.2007.01.024
166. Peruzzi D, Gavazza A, Mesiti G, Lubas G, Scarselli E, Conforti A, Bendtsen C, Ciliberto G, La Monica N, Aurisicchio L. A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma. Mol Ther 2010; 18:1559-67; PMID:20531395; http:// dx.doi.org/10.1038/mt.2010.104
167. Peruzzi D, Mesiti G, Ciliberto G, La Monica N, Aurisicchio L. Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs. Vaccine 2010; 28:1201-8; PMID:19944791; http://dx.doi. org/10.1016/j.vaccine.2009.11.031
168. 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
169. Greenland JR, Letvin NL. Chemical adjuvants for plasmid DNA vaccines. Vaccine 2007; 25:3731-41; PMID:17350735; http://dx.doi.org/10.1016/j. vaccine.2007.01.120
170. Vacchelli E, Prada N, Kepp O, Galluzzi L. Current trends of anticancer immunochemotherapy. Oncoimmunology 2013; 2:e25396; PMID:23894726; http://dx.doi.org/10.4161/ onci.25396