IMMUNOTHERAPY AND GENE THERAPY OF UVEAL MELANOMA

Abstract

One of the most important recent advances in the field of tumor immunology is the discovery of genes that encode tumor antigens. The immune system can recognize these antigens and has the potential of mobilizing effector T cells with the ability to completely eliminate progressively growing tumors. An obvious question raised by this discovery is, even though tumors express antigens that are recognized by the immune system, why do spontaneous tumors still develop and grow in patients? This question implies that antigens expressed on tumor cells are not immunogenic, or in other words, although tumor antigens are recognized by the immune system, they are unable to initiate protective immunity. It seems that tumors use a variety of different mechanisms to block the immune system from responding to antigens on tumor cells. Over the past decade several new cancer immunotherapies have been developed that attempt to bypass or overcome the tumor-associated blockade of protective immunity. Currently, there is renewed optimism these new approaches will be successful. Because the first tumor antigen genes identified were found in skin melanoma cells, most of the recent immunotherapies have focused initially on treating metastatic skin melanoma patients. In this article we will discuss our research on whether these approaches are appropriate for the treatment of uveal melanoma patients. First, however, we will review briefly the effector lymphocytes that participate in protective antitumor immunity, the genes identified that encode tumor antigens on skin melanomas, the conceptual basis for new cancer immunotherapies, and the status of current immunotherapies used to treat skin melanoma patients.