Metronomic cyclophosphamide enhances HPV16E7 peptide vaccine induced antigen-specific and cytotoxic T-cell mediated antitumor immune response

OncoImmunology

Volumn 3, Issue 8, 2014, Pages

  Weir, Genevieve M ^a,b   Hrytsenko, Olga ^a,b   Stanford, Marianne M ^a,b   Berinstein, Neil L ^c   Karkada, Mohan ^a,b   Liwski, Robert S ^b,d   Mansour, Marc ^a  

^a Immunovaccine Inc   (Canada)

^b DALHOUSIE UNIVERSITY   (Canada)

^c ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

^d QUEEN ELIZABETH II HEALTH SCIENCES CENTRE   (Canada)

Author keywords

Cancer; Checkpoint inhibitors; HPV16; Metronomic cyclophosphamide; Translational; Vaccine

Indexed keywords

ARGINYLALANYLHISTIDINYLASPARAGINYLISOLEUCYLVALYLTYROSYLTHREONYLISOLEUCYLPHENYLALANINE; ARGINYLALANYLHISTIDINYLASPARAGINYLISOLEUCYLVALYLTYROSYLTHREONYLISOLEUCYLPHENYLALANINE VACCINE; CANCER VACCINE; CHOLESTEROL; CYCLOPHOSPHAMIDE; DIOLEOYLPHOSPHATIDYLCHOLINE; MONTANIDE ISA 51; PEPTIDE VACCINE; PLACEBO; PROTEIN E7; UNCLASSIFIED DRUG;

ADD ON THERAPY; ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL INFILTRATION; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG FORMULATION; DRUG POTENTIATION; FEMALE; GENE OVEREXPRESSION; HUMAN PAPILLOMAVIRUS TYPE 16; IMMUNOGENICITY; IMMUNOMODULATION; IMMUNOSTIMULATION; IN VIVO STUDY; LIPOSOMAL DELIVERY; LOADING DRUG DOSE; LOW DRUG DOSE; LYMPHOCYTE DEPLETION; MALIGNANT NEOPLASTIC DISEASE; METRONOMIC DRUG ADMINISTRATION; MONOTHERAPY; MOUSE; MOUSE MODEL; MULTIPLE CYCLE TREATMENT; NONHUMAN; SPLEEN CELL; SUPPRESSOR CELL; TUMOR CELL INOCULATION; TUMOR MICROENVIRONMENT; TUMOR MODEL; TUMOR VIRUS; VIRUS CARCINOGENESIS;

EID: 84921648852     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/21624011.2014.953407     Document Type: Article

References (46)

1. Berzofsky, JA, Terabe, M, Wood, LV. Strategies to use immune modulators in therapeutic vaccines against cancer. Semin Oncol 2012; 39:348-57; PMID:22595057; http:// dx.doi.org/10.1053/j.seminoncol.2012.02.002
2. Weir, GM, Liwski, RS, Mansour, M. Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. Cancers (Basel) 2011; 3:3114-42; PMID:24212948; http://dx.doi.org/10.3390/cancers3033114
3. Karkada, M, Weir, GM, Quinton, T, Sammatur, L, MacDonald, LD, Grant, A, Liwski, R, Juskevicius, R, Sinnathamby, G, Philip, R, et al. A novel breast/ovarian cancer peptide vaccine platform that promotes specific type-1 but not Treg/Tr1-type responses. J Immunother 2010; 33:250-61; PMID:20445345; http://dx.doi.org/10.1097/CJI.0b013e3181c1f1e9
4. Daftarian, PM, Mansour, M, Pohajdak, B, Fuentes- Ortega, A, Korets-Smith, E, Macdonald, L, Weir, G, Brown, RG, Kast, WM. Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax encapsulated CTL/T helper peptides. J Transl Med 2007; 5:26; PMID:17555571; http://dx. doi.org/10.1186/1479-5876-5-26
5. Mansour, M, Pohajdak, B, Kast,WM, Fuentes-Ortega, A, Korets-Smith, E, Weir, GM, Brown, RG, Daftarian, P. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax. J Transl Med 2007; 5: 20; PMID:17451606; http://dx. doi.org/10.1186/1479-5876-5-20
6. Berinstein, NL, Karkada, M, Morse, MA, Nemunaitis, JJ, Chatta, G, Kaufman, H, Odunsi, K, Nigam, R, Sammatur, L,Macdonald, LD, et al. First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients. J Transl Med 2012; 10:156; PMID:22862954; http://dx.doi.org/ 10.1186/1479-5876-10-156
7. Galluzzi, L, Senovilla, L, Zitvogel, L, Kroemer, G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov 2012; 11:215-33; PMID:22301798; http://dx.doi.org/10.1038/nrd3626
8. Lutsiak, ME, Semnani, RT, De Pascalis, R, Kashmiri, SV, Schlom, J, Sabzevari, H. Inhibition of CD4(+) 25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005; 105:2862-8; PMID:15591121; http://dx. doi.org/10.1182/blood-2004-06-2410
9. Radojcic, V, Bezak, KB, Skarica, M, Pletneva, MA, Yoshimura, K, Schulick, RD, Luznik, L. Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunol Immunother 2009; 59:137-48; PMID:19590872; http://dx.doi.org/10.1007/s00262-009-0734-3
10. Schiavoni, G, Mattei, F, Di Pucchio, T, Santini, SM, Bracci, L, Belardelli, F, Proietti, E. Cyclophosphamide induces type I interferon and augments the number of CD44(hi) T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer. Blood 2000; 95:2024-30; PMID:10706870
11. Taieb, J, Chaput, N, Schartz, N, Roux, S, Novault, S, Menard, C, Ghiringhelli, F, Terme, M, Carpentier, AF, Darrasse-Jeze, G, et al. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J Immunol 2006; 176:2722-9; PMID:16493027; http://dx.doi.org/10.4049/jimmunol. 176.5.2722
12. Wada, S, Yoshimura, K, Hipkiss, EL, Harris, TJ, Yen, HR, Goldberg, MV, Grosso, JF, Getnet, D, Demarzo, AM, Netto, GJ, et al. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res 2009; 69:4309-18; PMID:19435909; http://dx.doi.org/10.1158/0008- 5472.CAN-08-4102
13. Audia, S, Nicolas, A, Cathelin, D, Larmonier, N, Ferrand, C, Foucher, P, Fanton, A, Bergoin, E, Maynadie, M, Arnould, L, et al. Increase of CD4+ CD25 +regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4 +CD25+ T lymphocytes. Clin Exp Immunol 2007; 150:523-30; PMID:17956583; http://dx.doi. org/10.1111/j.1365-2249.2007.03521.x
14. Vermeij, R, Leffers, N, Hoogeboom, BN, Hamming, IL, Wolf, R, Reyners, AK, Molmans, BH, Hollema, H, Bart, J, Drijfhout, JW, et al. Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: A single- arm phase II study. Int J Cancer 2011; 131:E670- 80; PMID:22139992; http://dx.doi.org/10.1002/ ijc.27388
15. Salem, ML, Kadima, AN, El-Naggar, SA, Rubinstein, MP, Chen, Y, Gillanders, WE, Cole, DJ. Defining the ability of cyclophosphamide preconditioning to enhance the antigen-specific CD8+ T-cell response to peptide vaccination: creation of a beneficial host microenvironment involving type I IFNs and myeloid cells. J Immunother 2007; 30:40-53; PMID:17198082; http://dx.doi.org/ 10.1097/01.cji.0000211311.28739.e3
16. Machiels, JP, Reilly, RT, Emens, LA, Ercolini, AM, Lei, RY, Weintraub, D, Okoye, FI, Jaffee, EM. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage- colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res 2001; 61:3689-97; PMID:11325840
17. Le, DT, Jaffee, EM. Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: a current perspective. Cancer Res 2012; 72:3439-44; PMID:22761338; http://dx.doi.org/10.1158/0008- 5472.CAN-11-3912
18. Browder, T, Butterfield, CE, Kraling, BM, Shi, B, Marshall, B, O'Reilly, MS, Folkman, J. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000; 60:1878-86; PMID:10766175
19. Man, S, Bocci, G, Francia, G, Green, SK, Jothy, S, Hanahan, D, Bohlen, P, Hicklin, DJ, Bergers, G, Kerbel, RS. Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 2002; 62:2731-5; PMID:12019144
20. Ghiringhelli, F, Menard, C, Puig, PE, Ladoire, S, Roux, S, Martin, F, Solary, E, Le Cesne, A, Zitvogel, L, Chauffert, B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007; 56:641-8; PMID:16960692; http://dx.doi.org/ 10.1007/s00262-006-0225-8
21. Smith, JS, Lindsay, L, Hoots, B, Keys, J, Franceschi, S, Winer, R, Clifford, GM. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 2007; 121:621-32; PMID:17405118; http://dx.doi. org/10.1002/ijc.22527
22. Ragin, CC, Modugno, F, Gollin, SM. The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 2007; 86:104-14; PMID:17251508; http://dx.doi.org/ 10.1177/154405910708600202
23. Welters, MJ, Kenter, GG, Piersma, SJ, Vloon, AP, Lowik, MJ, Berends-van der Meer, DM, Drijfhout, JW, Valentijn, AR, Wafelman, AR, Oostendorp, J, et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res 2008; 14:178-87; PMID:18172269; http://dx.doi.org/10.1158/1078- 0432.CCR-07-1880
24. Smyth, LJ, Van Poelgeest, MI, Davidson, EJ, Kwappenberg, KM, Burt, D, Sehr, P, Pawlita, M, Man, S, Hickling, JK, Fiander, AN, et al. Immunological responses in women with human papillomavirus type 16 (HPV-16)-associated anogenital intraepithelial neoplasia induced by heterologous prime-boost HPV- 16 oncogene vaccination. Clin Cancer Res 2004; 10:2954-61; PMID:15131030; http://dx.doi.org/ 10.1158/1078-0432.CCR-03-0703
25. Conesa-Zamora, P. Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape. Gynecol Oncol 2013; 131:480-8; PMID:23994536; http://dx.doi.org/10.1016/j.ygyno.2013.08.025
26. Peng, S, Lyford-Pike, S, Akpeng, B, Wu, A, Hung, CF, Hannaman, D, Saunders, JR, Wu, TC, Pai, SI. Lowdose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine. Cancer Immunol Immunother 2012; 62:171-82.
27. Feltkamp,MC, Smits, HL, Vierboom,MP,Minnaar, RP, de Jongh, BM, Drijfhout, JW, ter Schegget, J, Melief, CJ, Kast, WM. Vaccination with cytotoxic T lymphocyte epitope- containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 1993; 23:2242-9; PMID:7690326; http://dx. doi.org/10.1002/eji.1830230929
28. Wonderlich, J, Shearer, G, Livingstone, A, Brooks, A. Induction and measurement of cytotoxic T lymphocyte activity. Curr Protoc Immunol 2006; 3: Unit 3.11.
29. Guo, Q, Lv, Z, Fu, Q, Jiang, C, Liu, Y, Lai, L, Chen, Q, Shen, J,Wang, Q. IFN-gamma producing T cells contribute to the increase of myeloid derived suppressor cells in tumor-bearingmice after cyclophosphamide treatment. Int Immunopharmacol 2012; 12:425-32; PMID:22226750; http://dx.doi.org/10.1016/j.intimp.2011.12.016
30. Ugel, S, Peranzoni, E, Desantis, G, Chioda, M, Walter, S, Weinschenk, T, Ochando, JC, Cabrelle, A, Mandruzzato, S, Bronte, V. Immune tolerance to tumor antigens occurs in a specialized environment of the spleen. Cell Rep 2012; 2:628-39; PMID:22959433; http://dx.doi.org/10.1016/j.celrep.2012.08.006
31. Inozume, T, Hanada, K, Wang, QJ, Ahmadzadeh, M, Wunderlich, JR, Rosenberg, SA, Yang, JC. Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother 2010; 33: 956-64; PMID:20948441; http://dx.doi.org/ 10.1097/CJI.0b013e3181fad2b0
32. Salem, ML, Al-Khami, AA, El-Nagaar, SA, Zidan, AA, Al-Sharkawi, IM, Marcela Diaz-Montero, C, Cole, DJ. Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide. Cell Immunol 2012; 276:67-74; PMID:22560674; http://dx.doi.org/ 10.1016/j.cellimm.2012.03.010
33. Smith, PC Sladek, NE. Sensitivity of murine B- and Tlymphocytes to oxazaphosphorine and non-oxazaphosphorine nitrogen mustards. Biochem Pharmacol 1985; 34:3459-63; PMID:3876834; http://dx.doi.org/ 10.1016/0006-2952(85)90718-X
34. Balkwill, F, Montfort, A, Capasso, M. B regulatory cells in cancer. Trends Immunol 2013; 34(4):169-73.
35. Yanaba, K, Bouaziz, JD, Haas, KM, Poe, JC, Fujimoto, M, Tedder, TF. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T celldependent inflammatory responses. Immunity 2008; 28:639-50; PMID:18482568; http://dx.doi.org/ 10.1016/j.immuni.2008.03.017
36. Brodt, P, Gordon, J. Natural resistance mechanisms may play a role in protection against chemical carcinogenesis. Cancer Immunol Immunother 1982; 13:125- 7; PMID:6984356
37. Zhang, Y, Eliav, Y, Shin, SU, Schreiber, TH, Podack, ER, Tadmor, T, Rosenblatt, JD. B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. Cancer Immunol Immunother 2012; 62:87-99; PMID:22772949
38. Abes, R, Gelize, E, Fridman, WH, Teillaud, JL. Longlasting antitumor protection by anti-CD20 antibody through cellular immune response. Blood 2010; 116:926-34; PMID:20439625; http://dx.doi.org/ 10.1182/blood-2009-10-248609
39. Manzur, S, Cohen, S, Haimovich, J, Hollander, N. Enhanced therapeutic effect of B cell-depleting anti-CD20 antibodies upon combination with in-situ dendritic cell vaccination in advanced lymphoma. Clin Exp Immunol 2012; 170:291-9; PMID:23121670; http://dx.doi.org/10.1111/j.1365-2249.2012.04658.x
40. Ellebaek, E, Engell-Noerregaard, L, Iversen, TZ, Froesig, TM, Munir, S, Hadrup, SR, Andersen, MH, Svane, IM. Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide: results from a phase II trial. Cancer Immunol Immunother 2012; 61:1791-804; PMID:22426890; http://dx.doi.org/10.1007/s00262- 012-1242-4
41. Angulo, I, de las Heras, FG, Garcia-Bustos, JF, Gargallo, D, Munoz-Fernandez, MA, Fresno, M. Nitric oxide-producing CD11b(+)Ly-6G(Gr-1)(+) CD31(ER-MP12)(+) cells in the spleen of cyclophosphamide- treated mice: implications for T-cell responses in immunosuppressed mice. Blood 2000; 95:212-20; PMID:10607705
42. Tongu, M, Harashima, N, Monma, H, Inao, T, Yamada, T, Kawauchi, H, Harada, M. Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo. Cancer Immunol Immunother 2012; 62:383-91; PMID:22926062; http://dx.doi.org/10.1007/s00262- 012-1343-0
43. Mikyskova, R, Indrova, M, Pollakova, V, Bieblova, J, Simova, J, Reinis, M. Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloidderived suppressor cells induced by growing TC-1 tumors. J Immunother 2012; 35:374-84; PMID:22576342; http://dx.doi.org/10.1097/CJI. 0b013e318255585a
44. Song, X, Guo, W, Cui, J, Qian, X, Yi, L, Chang, M, Cai, Q, Zhao, Q. A tritherapy combination of a fusion protein vaccine with immune-modulating doses of sequential chemotherapies in an optimized regimen completely eradicates large tumors in mice. Int J Cancer 2010; 128:1129-38; http://dx.doi.org/10.1002/ ijc.25451
45. Bunt, SK, Clements, VK, Hanson, EM, Sinha, P, Ostrand-Rosenberg, S. Inflammation enhances myeloid- derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 2009; 85:996-1004; PMID:19261929; http://dx.doi.org/ 10.1189/jlb.0708446
46. Ostrand-Rosenberg, S Sinha, P. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009; 182:4499-506; PMID:19342621; http://dx. doi.org/10.4049/jimmunol.0802740