It has been shown in many animal models that tumor cells transduced to express B7 can be effective vaccines. Recent studies have shown that T-cell activation is even more complex than originally thought. The effectiveness of CTLA-4 treatment seems to correlate with the inherent immunogenicity of the tumor. It is of considerable interest that the majority of the mice develop a progressive hypopigmentation syndrome beginning a month or so after tumor rejection. This result suggests that the antigen responsible for the rejection may be a normal cell product involved in melanin synthesis, as has been shown in many human patients.
Efforts are underway to identify the target antigen.
Finally, we have begun to examine the effectiveness of CTLA-4 blockade in combination with conventional approaches to tumor therapy, including surgical reduction and chemotherapy. This work is in progress, but available data are quite promising.