In general, the proposed research is aimed at obtaining information that should make it possible to delineate some of the characteristics of a tumor system in which a low dose of melphalan is curative at an advanced stage of tumor growth. We know already that the curative effectiveness of a low dose of melphalan for mice bearing a large MOPC-315 plasmacytoma depends on the contribution of antitumor immunity in tumor eradication. We will determine whether a low dose of melphalan is curative also for mice bearing a large tumor of selected plasmacytomas that differ in their immunogenicity, thus eliciting varying degrees of antitumor immunity that can contribute to tumor eradication. For each of these tumors, we will establish a dose-response curve to determine the lowest dose of melphalan that is curative for mice at an advanced stage of tumor growth. In tumor models for which a low dose of melphalan is curative at an advanced stage of tumor growth, we will determine whether the curative effectiveness of the low dose of drug is due solely to the drug's tumoricidal activity or whether T-cell-dependent antitumor immunity also aids in tumor eradication. In tumor models for which a low dose of melphalan is not curative at an advanced stage of tumor growth, we will determine whether the failure of the low-dose chemotherapy to cure such mice is due to relative resistance of the tumor cells (as compared with the MOPC-315 cells) to the direct toxic effects of the drug and/or due to the development of an insufficient level of antitumor immunity to control the tumor burden that remains after clearance of the drug from the circulation. The information gathered from the proposed studies should make it possible to delineate some of the characteristics of a tumor system in which it might be possible to exploit host antitumor immunity therapeutically. (HF)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035761-02
Application #
3173339
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1984-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Overall Medical
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Ben-Efraim, S (1999) One hundred years of cancer immunotherapy: a critical appraisal. Tumour Biol 20:1-24
Ben-Efraim, S (1996) Cancer immunotherapy: hopes and pitfalls: a review. Anticancer Res 16:3235-40
Rubin, M; Mokyr, M B (1993) Characterization of the exogenous interleukin-2 requirements for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers. Cancer Immunol Immunother 36:37-44
Bartik, M M; Baumgartel-Scofield, B A; Mokyr, M B (1991) Enhanced expansion of the thymic CD8+ cell subset as a potential mechanism for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers. Cancer Immunol Immunother 34:79-89
Bartik, M M; Ahn, M C; Baumgartel, B A et al. (1990) Presence of an enlarged pool of MOPC-315-specific cytotoxic T lymphocyte precursors in the thymuses of mice that eradicated a large MOPC-315 tumor as a consequence of low-dose melphalan therapy. Cancer Immunol Immunother 32:143-53
Mokyr, M B; Barker, E; Weiskirch, L M et al. (1989) Importance of Lyt 2+ T-cells in the curative effectiveness of a low dose of melphalan for mice bearing a large MOPC-315 tumor. Cancer Res 49:4597-606
Barker, E; Wise, J A; Dray, S et al. (1989) Lysis of antigenically unrelated tumor cells mediated by Lyt 2+ splenic T-cells from melphalan-cured MOPC-315 tumor bearers. Cancer Res 49:5007-15
Wise, J A; Mokyr, M B; Dray, S (1989) Enhancement of the effectiveness of Lyt-2+ T-cells for adoptive chemoimmunotherapy by short-term exposure of tumor-bearer spleen cells to polyethylene glycol and/or melphalan. Cancer Res 49:3613-9
Mokyr, M B; Bartik, M M; Ahn, M C (1989) Interleukin 2 requirement for the in vitro generation of antitumor cytotoxicity by thymocytes from melphalan-cured MOPC-315 tumor bearers. Cancer Res 49:870-6
Dray, S; Mokyr, M B (1989) Cyclophosphamide and melphalan as immunopotentiating agents in cancer therapy. Med Oncol Tumor Pharmacother 6:77-85

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