Implications of apoptosis in cancer immunotherapy

Abstract

Inhibitions or blockages of ligand-receptor interactions on cancer cell surfaces by exogenous competetors or antibodies often result in apoptosis or “programmed cell death.” The underlying mechanisms of action for cellular apoptosis depend greatly on the molecular nature of specific ligand-receptor interactions and the signal transduction pathways involved. Two such unrelated systems which are potentially involved in apoptosis of cancer cells are described in this review. They are, respectively, gonadotropinreleasing hormone (GnRH) receptor and cancerous immunoglobulins, or CA215, both of which are widely expressed on the surface of cancer cells from diversified tissue origins. Bindings of GnRH or its decapeptide analogs as ligands to GnRH receptor were known to induce apoptosis of several extrapituitary cell types in gonadal tissues, as well as different cancer cells. Monoclonal antibodies against the GnRH receptor of cancer cells were shown to induce apoptosis, similar to the action of GnRH analogs. In contrast, RP215 monoclonal antibody reacts specifically with the carbohydrate-associated epitope of cancerous immunoglobulins and is known to induce apoptosis of cancer cells in vitro. It also causes growth inhibition of tumor cells in nude mouse experimental models. Elucidations of the specific mechanisms of apoptosis in cancer cells of these two molecular interaction systems will not only lead to a better understanding of cancer biology but also benefit patients in cancer monitoring and therapy.