Abstract
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.
Footnotes
-
↵1 Supported by Research Grant CA-76532 from the National Cancer Institute.
-
↵2 To whom requests for reprints should be addressed, at the Department of Biochemistry and Molecular Biology (M/C 536). The University of Illinois at Chicago, 1819 West Polk Street, Chicago, IL 60612. E-mail: Mokyr@uic.edu.
- Received September 2, 1998.
- Accepted October 19, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 23
