Immunologic targeting: how to channel a minimal response for maximal outcome

Drugs that target extracellular molecules and intracellular pathways remain an area of active research in prostate cancer. Although preclinical data suggest that new drugs can modulate or slow prostate tumor proliferation, responses in man, such as disease stabilization or regression, are not as dramatic as those seen in preclinical models. Other approaches, including carbohydrate and cellular product vaccines, cytokines, and monoclonal antibodies either alone or with radiopharmaceuticals, are being used to seek and destroy cancer cells. Although robust in-vitro antibody responses can be generated against a specific immunogen in many vaccines, immunologists would agree that immune responses are suboptimal, as defined by a lack of impact on tumor growth, and insufficient to impact on disease progression.

Although a preferred result, approaches that maximize the cellular arm of immune responses are limited by technology to detect these responses and by agents that can enhance their activity. DNA vaccines that target prostate-specific antigen and prostate-specific membrane antigen, and drugs that can block inhibitory molecules on T cells, such as cytotoxic T lymphocyte antigen-4, are currently under study.

This article will review state-of-the-art mechanisms by which immunity may be enhanced to elicit antitumor responses against selectively expressed cell surface molecules and to maximize antitumor responses.