Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

Cellular Immunology

Volumn 262, Issue 2, 2010, Pages 150-161

  Barbon, Christine M ^a   Yang, Min ^b   Wands, Gregory D ^b   Ramesh, Radha ^b   Slusher, Barbara S ^b   Hedley, Mary Lynne ^b   Luby, Thomas M ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b EISAI RESEARCH INSTITUTE   (United States)

Author keywords

Avidity; Cyclophosphamide; CYP1B1; Epitope spreading; Immunization; PLG; Poly(lactide co glycolide); Regulatory T cell; Treg; Vaccine

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; CYCLOPHOSPHAMIDE; CYTOCHROME P450 1B1; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DNA VACCINE; EPITOPE; POLYLACTIDE; TRANSCRIPTION FACTOR FOXP3; TUMOR ANTIGEN; UNCLASSIFIED DRUG; ZYC 300;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG MEGADOSE; DRUG POTENTIATION; DRUG TARGETING; EFFECTOR CELL; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOTHERAPY; LOW DRUG DOSE; LYMPHOCYTE COUNT; MALIGNANT NEOPLASTIC DISEASE; MICROENCAPSULATION; MOUSE; MULTIPLE CYCLE TREATMENT; NONHUMAN; PRIORITY JOURNAL; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SINGLE DRUG DOSE; SPLEEN CELL; T LYMPHOCYTE;

ANIMALS; ANTIGENS, NEOPLASM; ARYL HYDROCARBON HYDROXYLASES; CELL LINE; CYCLOPHOSPHAMIDE; DRUG COMPOUNDING; EPITOPES; FEMALE; HUMANS; IMMUNIZATION; IMMUNOSUPPRESSIVE AGENTS; MICE; MICE, INBRED C3H; SPLEEN; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; VACCINES, DNA;

MUS;

EID: 77950866195     PISSN: 00088749     EISSN: 10902163     Source Type: Journal    
DOI: 10.1016/j.cellimm.2010.02.007     Document Type: Article

References (73)

1. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155:1151-1164.
2. Sakaguchi S., Sakaguchi N. Regulatory T cells in immunologic self-tolerance and autoimmune disease. Int. Rev. Immunol. 2005, 24:211-226.
3. Takahashi T., Kuniyasu Y., Toda M., Sakaguchi N., Itoh M., Iwata M., Shimizu J., Sakaguchi S. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 1998, 10:1969-1980.
4. Shevach E.M. Certified professionals: CD4(+)CD25(+) suppressor T cells. J. Exp. Med. 2001, 193:F41-F46.
5. Shevach E.M. Mechanisms of Foxp3+ T regulatory cell-mediated suppression. Immunity 2009, 30:636-645.
6. Grossman W.J., Verbsky J.W., Barchet W., Colonna M., Atkinson J.P., Ley T.J. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004, 21:589-601.
7. Miyara M., Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol. Med. 2007, 13:108-116.
8. Levings M.K., Bacchetta R., Schulz U., Roncarolo M.G. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int. Arch. Allergy Immunol. 2002, 129:263-276.
9. You S., Thieblemont N., Alyanakian M.A., Bach J.F., Chatenoud L. Transforming growth factor-beta and T-cell-mediated immunoregulation in the control of autoimmune diabetes. Immunol. Rev. 2006, 212:185-202.
10. Roncarolo M.G., Gregori S., Battaglia M., Bacchetta R., Fleischhauer K., Levings M.K. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 2006, 212:28-50.
11. Taylor A., Verhagen J., Blaser K., Akdis M., Akdis C.A. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 2006, 17:433-442.
12. Curti A., Pandolfi S., Valzasina B., Aluigi M., Isidori A., Ferri E., Salvestrini V., Bonanno G., Rutella S., Durelli I. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 2007, 109:2871-2877.
13. Eddahi R., Oldenhove G., Denanglaire S., Urbain J., Leo O., Andris F. CD4+ CD25+ regulatory T cells control the magnitude of T-dependent humoral immune responses to exogenous antigens. Eur. J. Immunol. 2006, 36:855-863.
14. Zhao Y. The two simultaneously occurring processes in one immune response: the positive immune reaction and immune tolerance. Med. Hypotheses 2006, 67:1384-1385.
15. Bennett C., Christie J., Ramsdell F., Brunkow M., Ferguson P., Whitesell L., Kelly T., Saulsbury F.T., Chance P.F., Ochs H.D. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001, 27:20-21.
16. Brunkow M., Jeffery E., Hjerrild K., Paeper B., Clark L., Yasayko S., Wilkinson J., Galas D., Ziegler S.F., Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001, 27:68-73.
17. Jordan M.S., Boesteanu A., Reed A.J., Petrone A.L., Holenbeck A.E., Lerman M.A., Naji A., Caton A.J. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2001, 2:301-306.
18. Akbar A.N., Taams L.S., Salmon M., Vukmanovic-Stejic M. The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology 2003, 109:319-325.
19. Valzasina B., Piconese S., Guiducci C., Colombo M.P. Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer Res. 2006, 66:4488-4495.
20. Colombo M.P., Piconese S. Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat. Rev. Cancer 2007, 7:880-887.
21. Liyanage U.K., Moore T.T., Joo H.G., Tanaka Y., Herrmann V., Doherty G., Drebin J.A., Strasberg S.M., Eberlein T.J., Goedegebuure P.S., Linehan D.C. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol. 2002, 169:2756-2761.
22. Ghiringhelli F., Larmonier N., Schmitt E., Parcellier A., Cathelin D., Garrido C., Chauffert B., Solary E., Bonnotte B., Martin F. 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. 2004, 34:336-344.
23. Curiel T.J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., Evdemon-Hogan M., Conejo-Garcia J.R., Zhang L., Burow M., Zhu Y., Wei S., Kryczek I., Daniel B B., Gordon A., Myers L., Lackner A., Disis M.L., Knutson K.L., Chen L., Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 2004, 10:942-949.
24. Viguier M., Lemaître F., Verola O., Cho M.S., Gorochov G., Dubertret L., Bachelez H., Kourilsky P., Ferradini L. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J. Immunol. 2004, 173:1444-1453.
25. Grauer O.M., Nierkens S., Bennink E., Toonen L.W., Boon L., Wesseling P., Sutmuller R.P., Adema G.J. CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int. J. Cancer 2007, 121:95-105.
26. Brode S., Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit. Rev. Immunol. 2008, 28:109-126.
27. Brock N., Wilmanns H. Effect of a cyclic nitrogen mustard-phosphamidester on experimentally induced tumors in rats; chemotherapeutic effect and pharmacological properties of B 518 ASTA (article in German). Dtsch. Med. Wochenschr. 1958, 83:453-458.
28. Berd D., Mastrangelo M.J., Engstrom P.F., Paul A., Maguire H. Augmentation of the human immune response by cyclophosphamide. Cancer Res. 1982, 42:4862-4866.
29. Maguire H.C., Ettore V.L. Enhancement of dinitrochlorobenzene (DNCB) contact sensitization by cyclophosphamide in the guinea pig. J. Invest. Dermatol. 1967, 48:29-43.
30. Maguire H.C. Specific acquired immune unresponsiveness to contact allergens with cyclophosphamide in the mouse. Int. Arch. Allergy Appl. Immunol. 1976, 50:651-658.
31. Polak L., Turk J.L. Reversal of immunological tolerance by cyclophosphamide through inhibition of suppressor cell activity. Nature 1974, 249:654-656.
32. Schwartz A., Askenase P.W., Gershon R.K. Regulation of delayed-type hypersensitivity reactions by cyclophosphamide-sensitive T cells. J. Immunol. 1978, 121:1573-1577.
33. Hermans I.F., Chong T.W., Palmowski M.J., Harris A.L., Cerundolo V. Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model. Cancer Res. 2003, 63:8408-8413.
34. Lutsiak M.E.C., Semnani R.T., De Pascalis R., Kashmiri S.V.S., Schlom J., Sabzevari H. Inhibition of CD4+ 25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005, 105:2862-2868.
35. Taieb J., Chaput N., Schartz N., Roux S., Novault S., Ménard C., Ghiringhelli F., Terme M., Carpentier A.F., Darrasse-Jèse G., Lemonnier F., Zitvogel L. Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines. J. Immunol. 2006, 176:2722-2729.
36. Berraondo P., Nouzé C., Préville X., Ladant D., Leclerc C. Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive, and regulatory components of the immune system. Cancer Res. 2007, 67:8847-8855.
37. Wada S., Yoshimura K., Hipkiss E.L., Harris T.J., Yen H.R., Goldberg M.V., Grosso J.F., Getnet D., Demarzo A.M., Netto G.J. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res. 2009, 69:4309-4318.
38. Ghiringhelli F., Menard C., Puig P.E., 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, 56:641-648.
39. L.M. Nadler, N. Haining, L. Drury, P. Enzinger, K. Russell, G. Weems, L. Hughes, T.M. Luby, M. Matijevic, R. Ramesh, M.L. Hedley, J. Gong, N. Tannir, D. Hong, R. Kurzrock Anti-CYP1B1 biologic and clinical responses are induced in patients with advanced stage solid tumors with cyclophosphamide pre-dosing and immunization with ZYC300. 99th AACR Annual Meeting (2008) Abstract # 2544.
40. Proietti E., Greco G., Garrone B., Baccarini S., Mauri C., Venditti M., Carlei D., Belardelli F. Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice. J. Clin. Invest. 1998, 2:429-441.
41. Bracci L., Moschella F., Sestili P., La Sorsa V., Valentini M., Canini I., Baccarini S., Maccari S., Ramoni C., Belardelli F. 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. 2007, 3:644-653.
42. Murray G.I., Taylor M.C., McFadyen M.C.E., McKay J.A., Greenlee W.F., Burke M.D., Melvin W.T. Tumor-specific expression of cytochrome P450 CYP1B1. Cancer Res. 1997, 57:3026-3031.
43. McFadyen M.C.E., Breeman S., Payne S., Stirk C., Miller I.D., Melvin W.T., Miller G.I. Immunohistochemical localization of cytochrome P450 CYP1B1 in breast cancer with monoclonal antibodies specific for CYP1B1. J. Histochem. Cytochem. 1999, 47:1457-1464.
44. Maecker D.H., Sherr R.H., Vonderheide M.S., von Bergwelt-Baildon M.S., Hirano N., Anderson K.S., Xia Z., Butler M.O., Wucherpfennig K.W., O'Hara C., Cole G., Kwak S.S., Ramstedt U., Tomlinson A.J., Chicz R.M., Nadler L.M., Schultze J.L. The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells. Blood 2003, 102:3287-3294.
45. Luby T.M., Cole G., Baker L., Kornher J.S., Ramstedt U., Hedley M.L. Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1. Clin. Immunol. 2004, 112:45-53.
46. Luby T.M. Targeting cytochrome P450 CYP1B1 with a therapeutic cancer vaccine. Expert Rev. Vaccines 2008, 7:995-1003.
47. Hedley M.L., Strominger J.L., Urban R.G. Plasmid DNA encoding targeted naturally processed peptides generates protective cytotoxic T lymphocyte responses in immunized animals. Hum. Gene Ther. 1998, 9:325-332.
48. McKeever U., Barman S., Hao T., Chambers P., Song S., Lunsford L., Hsu Y.-Y., Roy K., Hedley M.L. Protective immune responses elicited in mice by immunization with formulations of poly(lactide-co-glycolide) microparticles. Vaccine 2002, 20:1524-1531.
49. Gribben J.G., Ryan D.P., Boyajian G., Urban R.G., Hedley M.L., Beach K., Nealon P., Matulonis U., Campos S., Gilligan T.D. Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin. Cancer Res. 2005, 11:4430-4544.
50. Shimizu J., Yamazaki S., Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 1999, 163:5211-5218.
51. Sakaguchi S., Sakaguchi N., Shimizu J., Yamazaki S., Sakihama T., Itoh M., Kuniyasu Y., Nomura T., Toda M., Takahashi T. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 2001, 182:18-32.
52. Walker L.S.K., Abbas A.K. The enemy within: keeping self-reactive T cells at bay in the periphery. Nat. Rev. Immunol. 2002, 2:11-19.
53. Emens L.A., Reilly R.T., Jaffee E.M. Breast cancer vaccines: maximizing cancer treatment by tapping into host immunity. Endocr. Relat. Cancer 2005, 12:1-17.
54. Nava-Parada P., Forni G., Knutson K.L., Pease L.R., Celis E. Peptide vaccine given with a toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors. Cancer Res. 2007, 67:1326-1334.
55. Shaked Y., Emmenegger U., Francia G., Chen L., Lee C.R., Man S., Paraghamian A., Ben-David Y., Kerbel R.S. Low-dose metronomic combined with intermittent bolus-dose cyclophosphamide is an effective long-term chemotherapy treatment strategy. Cancer Res. 2005, 65:7045-7051.
56. Matsushita N., Pilon-Thomas S.A., Martin L.M., Riker A.I. Comparative methodologies of regulatory T cell depletion in a murine melanoma model. J. Immunol. Methods 2008, 333:167-179.
57. Motoyoshi Y., Kaminoda K., Saitoh O., Hamasaki K., Nakao K., Ishii K., Nagayama Y., Eguchi K. Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol. Rep. 2006, 16:141-146.
58. Gallelli J.F. Stability studies of drugs used in intravenous solutions. Am. J. Hosp. Pharm. 1967, 24:425-433.
59. Brooke D., Bequette R.J., Davis R.E. Chemical stability of cyclophosphamide in parenteral solutions. Am. J. Hosp. Pharm. 1973, 30:134-137.
60. Walker L.S., Chodos A., Eggena M., Dooms H., Abbas A.K. Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo. J. Exp. Med. 2003, 198:249-258.
61. Billiard F., Litvinova E., Saadoun D., Djelti F., Klatzmann D., Cohen J.L., Marodon G., Salomon B.L. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J. Immunol. 2006, 77:2167-2174.
62. Ercolini A.M., Ladle B.H., Manning E.A., Pfannenstiel L.W., Armstrong T.D., Machiels J.P., Bieler J.G. Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J. Exp. Med. 2005, 201:1591-1602.
63. Z. Lu, D.H. Sherr, A head-to head comparison between cyclophosphamide and Ontak in reducing the influence of Tregs on self (tumor) peptide-specific CTL responses. 50th Annual American Society of Hematology (2008) Abstract # 2570.
64. Emens L.A., Jaffee E.M. Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res. 2005, 65:8059-8064.
65. de Visser K.E., Eichten A., Coussens L.M. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 2006, 6:24-37.
66. McMahan R.H., Slansky J.E. Mobilizing the low-avidity T cell repertoire to kill tumors. Semin. Cancer Biol. 2007, 17:317-329.
67. Yee C., Savage P.A., Lee P.P., Davis M.M., Greenberg P.D. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J. Immunol. 1999, 162:2227-2234.
68. Zeh H.J., Perry-Lalley D., Dudley M.E., Rosenberg S.A., Yang J.C. High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. J. Immunol. 1999, 162:989-994.
69. Derby M., Alexander-Miller M., Tse R., Berzofsky J. High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL. J. Immunol. 2001, 166:1690-1697.
70. Garcia-Lora A., Algarra I., Garrido F. MHC class I antigens, immune surveillance, and tumor escape. J. Cell. Physiol. 2003, 195:346-355.
71. Bubeník J. MHC class I down-regulation: tumour escape from immune surveillance?. Int. J. Oncol. 2004, 25:487-491.
72. Drake C.G., Jaffee E., Pardoll D.M. Mechanisms of immune evasion by tumors. Adv. Immunol. 2006, 90:51-81.
73. Ruter J., Barnett B.G., Kryczek I., Brumlik M.J., Daniel B.J., Coukos G., Zou W., Curiel T.J. Altering regulatory T cell function in cancer immunotherapy: a novel means to boost the efficacy of cancer vaccines. Front. Biosci. 2009, 14:1761-1770.