Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

Cancer Immunology, Immunotherapy

Volumn 62, Issue 1, 2013, Pages 171-182

  Peng, Shiwen ^a   Lyford Pike, Sofia ^a   Akpeng, Belinda ^a   Wu, Annie ^a   Hung, Chien Fu ^a   Hannaman, Drew ^b   Saunders, John R ^a,c   Wu, T C ^a   Pai, Sara I ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Ichor Medical Systems Inc   (United States)

^c GREATER BALTIMORE MEDICAL CENTER   (United States)

Author keywords

Cyclophosphamide; Head and neck cancer; Human papillomavirus; Immunomodulatory agents; Regulatory T cells; Vaccine

Indexed keywords

CYCLOPHOSPHAMIDE; DNA VACCINE; PHOSPHORYL LIPID A; PLACEBO; TRANSCRIPTION FACTOR FOXP3; WART VIRUS VACCINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFECT; DRUG POTENTIATION; DRUG TARGETING; LOW DRUG DOSE; MOLECULAR DYNAMICS; MONOTHERAPY; MOUSE; NONHUMAN; OPTIMAL DRUG DOSE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SINGLE DRUG DOSE; TREND STUDY; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CANCER VACCINES; CD8-POSITIVE T-LYMPHOCYTES; COMBINED MODALITY THERAPY; CYCLOPHOSPHAMIDE; FLOW CYTOMETRY; MICE; MICE, INBRED C57BL; NEOPLASMS, EXPERIMENTAL; PAPILLOMAVIRUS VACCINES; VACCINES, DNA;

EID: 84872485478     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-012-1322-5     Document Type: Article

References (44)

1. Gillison ML, Koch WM, Capone RB et al (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709-720
2. Chung CH, Gillison ML (2009) Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res 15(22):6758-6762
3. Wu AA, Niparko KJ, Pai SI (2008) Immunotherapy for head and neck cancer. J Biomed Sci 15:275-289
4. Trimble CL, Peng S, Kos F et al (2009) A phase I trial of a human papillomavirus DNA vaccine for HPV16 + cervical intraepithelial neoplasia 2/3. Clin Cancer Res 15:361-367
5. Kenter GG, Welters MJ, Valentijn AR et al (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838-1847
6. Radulovic S, Brankovic-Magic M, Malisic E et al (2009) Therapeutic cancer vaccines in cervical cancer: phase I study of Lovaxin-C. J BUON 14(Suppl 1):S165-S168
7. Emens LA, Reilly RT, Jaffee EM (2005) Cancer vaccines in combination with multimodality therapy. Cancer Treat Res 123:227-245
8. Andersen MH, Sørensen RB, Schrama D et al (2008) Cancer treatment: the combination of vaccination with other therapies. Cancer Immunol Immunother 57(11):1735-1743
9. Machiels JP, Reilly RT, Emens LA et al (2001) 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 61:3689-3697
10. Emens LA, Armstrong D, Biedrzycki B et al (2004) A phase I vaccine safety and chemotherapy dose-finding trial of an allogeneic GM-CSF-secreting breast cancer vaccine given in a specifically timed sequence with immunomodulatory doses of cyclophosphamide and doxorubicin. Hum Gene Ther 15:313-337
11. Bass KK, Mastrangelo MJ (1998) Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol Immunother 47:1-12
12. Mastrangelo MJ, Berd D, Maguire H Jr (1986) The immunoaugmenting effects of cancer chemotherapeutic agents. Semin Oncol 13:186-194
13. Wada S, Yoshimura K, Hipkiss EL et al (2009) Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res 69:4309-4318
14. Ghiringhelli F, Larmonier N, Schmitt E et al (2004) CD4 + CD25 + regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34:336-344
15. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H (2005) Inhibition of CD4(+)25 + T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105:2862-2868
16. Josefowicz SZ, Lu LF, Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30:531-564
17. Albers AE, Ferris RL, Kim GG, Chikamatsu K, DeLeo AB, Whiteside TL (2005) Immune responses to p53 in patients with cancer: enrichment in tetramer + p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol Immunother 54:1072-8118
18. Lin KY, Guarnieri FG, Staveley-O'Carroll KF et al (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56:21-26
19. Kim JW, Hung CF, Juang J, He L, Kim TW, Armstrong DK, Pai SI, Chen PJ, Lin CT, Boyd DA, Wu TC (2004) Comparison of HPV DNA vaccines employing intracellular targeting strategies. Gene Ther 11(12):1011-1018
20. Münger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM (1989) Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 8(13):4099-4105
21. Jurk M, Vollmer J (2007) Therapeutic applications of synthetic CpG oligodeoxynucleotides as TLR9 agonists for immune modulation. BioDrugs 21:387-401
22. Luxembourg A, Hannaman D, Ellefsen B, Nakamura G, Bernard R (2006) Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 24:4490-4493
23. Mir O, Domont J, Cioffi A et al (2011) Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma. Eur J Cancer 47:515-519
24. Lord R, Nair S, Schache A et al (2007) Low dose metronomic oral cyclophosphamide for hormone resistant prostate cancer: a phase II study. J Urol 177:2136-2140
25. Sato E, Olson SH, Ahn J et al (2005) Intraepithelial CD8 + tumor-infiltrating lymphocytes and a high CD8 +/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102(51):18538-18543
26. Piersma SJ, Jordanova ES, van Poelgeest MI et al (2007) High number of intraepithelial CD8 + tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer. Cancer Res 67(1):354-361
27. Angulo I, de las Heras FG, García-Bustos JF, Gargallo D, Muñoz-Fernández MA, Fresno M (2000) 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 95(1):212-220
28. Mikyšková R, Indrová M, Polláková V, Bieblová J, Símová J, Reiniš M (2012) Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors. J Immunother 35(5):374-384
29. Leao IC, Ganesan P, Armstrong TD, Jaffee EM (2008) Effective depletion of regulatory T cells allows the recruitment of mesothelin-specific CD8 T cells to the antitumor immune response against a mesothelin-expressing mouse pancreatic adenocarcinoma. Clin Transl Sci 1(3):228-239
30. Kerbel RS, Kamen BA (2004) The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4(6):423-436
31. Bracci L, Moschella F, Sestili P et al (2007) Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, B-cell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin Cancer Res 13:644-653
32. Berraondo P, Nouze C, Preville X, Ladant D, Leclerc C (2007) Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive, and regulatory components of the immune system. Cancer Res 67:8847-8855
33. Damber JE, Vallbo C, Albertsson P, Lennernas B, Norrby K (2006) The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin. Cancer Chemother Pharmacol 58:354-360
34. Man S, Bocci G, Francia G et al (2002) Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 62:2731-2735
35. Burton JH, Mitchell L, Thamm DH, Dow SW, Biller BJ (2011) Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma. J Vet Intern Med 25(4):920-926
36. Khan OA, Blann AD, Payne MJ et al (2011) Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer. Br J Cancer 104(12):1822-1827
37. Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105:1045-1047
38. Sanchez-Munoz A, Mendiola C, Perez-Ruiz E et al (2010) Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Oncology 79(1-2):98-104
39. Colleoni M, Rocca A, Sandri MT et al (2002) Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann Oncol 13:73-80
40. Reinhardt J, Schott S, Mayer C, Sohn C, Eichbaum M (2011) Long-term remission of an advanced recurrent endometrial cancer in a heavily pretreated patient using a combined regimen with bevacizumab and metronomic cyclophosphamide. Anticancer Drugs 22:822-824
41. Ladoire S, Eymard JC, Zanetta S et al (2010) Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure. Anticancer Res 30(10):4317-4323
42. Hermans IF, Chong TW, Palmowski MJ, Harris AL, Cerundolo V (2003) Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model. Cancer Res 63:8408-8413
43. Ghiringhelli F, Menard C, Puig PE et al (2007) 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 56:641-648
44. Emens LA, Asquith JM, Leatherman JM et al (2009) Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol 27:5911-5918