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Cyclophosphamide and melphalan as immunopotentiating agents in cancer therapy

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Abstract

The murine plasmacytoma, MOPC-315, has been used as a tumor model to investigate the immunopotentiating effect of a low dose of cyclophosphamide (CY) or melphalan (l-PAM). Each drug was shown to shift the balance in mice bearing a late-stage tumor from a state of immunosuppression to that of potent T-cell-dependent antitumor immunity against tumor-associated antigens. The resultant immunity eradicated the extensive tumor burden not already eradicated by the direct tumoricidal activity of the drug and brought about the cure of the mice. The immunity responsible for tumor eradication, as well as the immunity responsible for the resistance of the cured mice to further tumor challenge, was mediated by the Lyt 2 subset of T-cells which contains cytotoxic T-cells. The principle of using a low dose of drug to selectively decrease suppressor cell activity so as to allow the development of antitumor immunity with the aid of autologous tumor vaccine or interleukin-2 has been exploited successfully by clinicians in therapeutic protocols for human melanoma.

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References

  1. Mathe G, Halle-Pannenko O, Bourut C: Effectiveness of murine leukemia chemotherapy according to the immune state.Cancer Immun Immunother 2, 39 (1977).

    Google Scholar 

  2. Lubet R A, Carlson D E: Therapy of murine plasmacytoma MOPC 104E: role of the immune response.J natn Cancer Inst 61, 897 (1978).

    CAS  Google Scholar 

  3. Hengst J C D, Mokyr M B, Dray S: Importance of timing of cyclophosphamide therapy of MOPC-315 tumor bearing mice.Cancer Res 40, 2135 (1980).

    PubMed  CAS  Google Scholar 

  4. Mokyr M B, Dray S: Some advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with a low rather than a high dose of cyclophosphamide.Cancer Res 43, 3112 (1983).

    PubMed  CAS  Google Scholar 

  5. Hilgard P, Pohl J, Stekar J, Voegeli R: Oxazaphosphorines as biological response modifiers: experimental and clinical perspectives.Cancer Treat Rep 12, 155 (1985).

    Article  CAS  Google Scholar 

  6. Hengst J C D, Mokyr M B, Dray S: Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors.Cancer Res 41, 2163 (1981).

    PubMed  CAS  Google Scholar 

  7. Ben-Efraim S, Bocian R C, Mokyr M B, Dray S: Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytoma tumor growth.Cancer Immun Immunother 15, 101 (1983).

    CAS  Google Scholar 

  8. Mokyr M B, Dray S: Interplay between the toxic effects of anticancer drugs and host antitumor immunity in cancer therapy.Cancer Invest 5, 31 (1987).

    Article  PubMed  CAS  Google Scholar 

  9. Mokyr M B, Hengst J C D, Dray S: Role of antitumor immunity in cyclophosphamide-induced rejection of subcutaneous MOPC-315 tumors.Cancer Res 42, 974 (1982).

    PubMed  CAS  Google Scholar 

  10. Barker E, Mokyr M B: Importance of Lyt 2+ T-cells in the resistance of melphalan cured MOPC-315 tumor bearers to a challenge with MOPC-315 tumor cells.Cancer Res 48, 4834 (1988).

    PubMed  CAS  Google Scholar 

  11. Barker E, Mokyr M B: Some characteristics of thein vivo antitumor immunity exhibited by mice cured of a large MOPC-315 tumor by a low dose of melphalan.Cancer Immun Immunother 25, 215 (1987).

    CAS  Google Scholar 

  12. North R J: Down-regulation of antitumor immune responses.Adv Cancer Res 45, 1 (1985).

    Article  PubMed  CAS  Google Scholar 

  13. Mokyr M B, Braun D P, Usher D, Reiter H, Dray S: The development ofin vitro andin vivo anti-tumor cytotoxicity in noncytotoxic, MOPC-315-tumorbearer, spleen cells “educated”in vitro with MOPC-315 tumor cells.Cancer Immun Immunother 4, 143 (1978).

    Article  Google Scholar 

  14. Mokyr M B, Braun D P, Dray S: Augmentation of antitumor cytotoxicity in MOPC-315 tumor bearer spleen cells by depletion of glass-adherent cells prior toin vitro activation.Cancer Res 39, 785 (1979).

    PubMed  CAS  Google Scholar 

  15. Bocian R C, Ben-Efraim S, Dray S, Mokyr M B: Melphalan-mediated potentiation of antitumor immune responsiveness of immunosuppressed spleen cells from mice bearing a large MOPC-315 tumor.Cancer Immun Immunother 18, 41 (1984).

    CAS  Google Scholar 

  16. Ye Q-W, Mokyr M B, Pyle J M, Dray S: Suppression of antitumor immunity by macrophages in spleens of mice bearing a large MOPC-315 tumor.Cancer Immun Immunother 16, 162 (1984).

    CAS  Google Scholar 

  17. Mokyr M B, Colvin M, Dray S: Cyclophosphamidemediated enhancement of antitumor immune potential of immunosuppressed spleen cells from mice bearing a large MOPC-315 tumor.Int J Immunopharmac 7, 111 (1985).

    Article  CAS  Google Scholar 

  18. Bocian R C, Dray S, Ben-Efraim S, Mokyr M B: Melphalan-induced enhancement of tumor cell immunostimulatory capacity as a mechanism for the appearance of potent antitumor immunity in the spleen of mice bearing a large metastatic MOPC-315 tumor.Cancer Immun Immunother 20, 61 (1985).

    CAS  Google Scholar 

  19. Berd D, Maguire H C, Mastrangelo M J: Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide.Cancer Res 46, 2572 (1986).

    PubMed  CAS  Google Scholar 

  20. Berd D, Mastrangelo M J: Active immunotherapy of human melanoma exploiting the immunopotentiating effects of cyclophosphamide.Cancer Invest 6, 335 (1988).

    Article  Google Scholar 

  21. Mitchell M S, Kempf R A, Harel W, Shau H, Boswell W D, Lind S, Bradley E C: Effectiveness and tolerability of low-dose cyclophosphamide and lowdose intravenous interleukin-2 in disseminated melanoma.J clin Oncol 6, 409 (1988).

    PubMed  CAS  Google Scholar 

  22. DiGiacomo A, North R J: T cell suppressors of antitumor immunity: the production of Lyt 12+ suppressors of delayed sensitivity precedes the production of suppressors of protective immunity.J exp Med 164, 1179 (1986).

    Article  PubMed  CAS  Google Scholar 

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Dray, S., Mokyr, M.B. Cyclophosphamide and melphalan as immunopotentiating agents in cancer therapy. Med. Oncol. & Tumor Pharmacother. 6, 77–85 (1989). https://doi.org/10.1007/BF02985227

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