Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in
cancers of different origin in which they enhance the survival of the
cancer cells. Consequently, they represent prime candidates for anti-
cancer therapy and specific
antisense oligonucleotides or small molecule inhibitors have shown broad anti-
cancer activities in pre-clinical models and are currently tested in clinical trials. In addition, immune-mediated
tumor destruction is emerging as an interesting modality to treat
cancer patients. Notably, spontaneous cellular immune responses against the Bcl-2 family
proteins have been identified as frequent features in
cancer patients underscoring that these
proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti-
cancer immunotherapeutic strategies, alone or in the combination with conventional
therapy. Here, we summarize the current knowledge of Bcl-2 family
proteins as T-cell
antigens, which has set the stage for the first explorative trial using these
antigens in therapeutic vaccinations against
cancer, and discuss future opportunities.