The universal character of the tumor-associated antigen survivin.

Abstract

Survivin is expressed in most human neoplasms, but is absent in normal, differentiated tissues. Survivin is a bifunctional inhibitor of apoptosis protein that has been implicated in protection from apoptosis and regulation of mitosis. Several clinical trials targeting survivin with a collection of different approaches from small molecule antagonists to immunotherapy are currently under way. With regard to the latter, spontaneous anti-survivin T-cell reactivity has been described in cancer patients suffering from a huge range of cancers of different origin, e.g., breast and colon cancer, lymphoma, leukemia, and melanoma. Thus, survivin may serve as a universal target antigen for anticancer immunotherapy. Accordingly, down-regulation of survivin as a means of immune escape would severely inflict the survival capacity of tumor cells, which highlights this protein as a prime target candidate for therapeutic vaccinations against cancer. Data from several ongoing phase I/II trials targeting survivin for patients with advanced cancer will provide further information about this idea.