RT Journal Article
SR Electronic
T1 Realization of the Therapeutic Potential of CTLA-4 Blockade in Low-Dose Chemotherapy-treated Tumor-bearing Mice
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 5301
OP 5304
VO 58
IS 23
A1 Mokyr, Margalit B.
A1 Kalinichenko, Tatiana
A1 Gorelik, Leonid
A1 Bluestone, Jeffrey A.
YR 1998
UL http://cancerres.aacrjournals.org/content/58/23/5301.abstract
AB CTLA-4 blockade has been shown by other investigators [D. R. Leach, et al., Science (Washington DC), 271: 1734–1736, 1996; and Y-F. Yang, et al., Cancer Res., 57: 4036–4041, 1997] to retard tumor growth in selected tumor systems. Here, we show that CTLA-4 blockade alone was ineffective in retarding tumor growth in the murine MOPC-315 tumor system. Yet, CTLA-4 blockade offered significant therapeutic benefits to MOPC-315 tumor bearers when combined with a subtherapeutic dose of the chemotherapeutic agent melphalan, which was previously shown (L. Gorelik, et al., Cancer Immunol. Immunother., 39: 117–126, 1994) to shift the cytokine profile in the tumor bearers toward type-1 cytokines. In addition, we show here that anti-CTLA-4 monoclonal antibody enhanced antitumor cytotoxicity when the anti-CTLA-4 monoclonal antibody was added to stimulation cultures of spleen cells from low-dose melphalan-treated MOPC-315 tumor-bearing mice but not from untreated tumor-bearing mice. These results suggest that the therapeutic benefits of CTLA-4 blockade depend on the ability of drugs such as melphalan to promote an immunogenic environment by altering the cytokine profile of tumor-specific T cells. ©1998 American Association for Cancer Research.