Development of antibodies and chimeric molecules for cancer immunotherapy.

Monoclonal antibodies are among the most rapidly expanding class of therapeutics for cancer treatment. Monoclonal antibodies targeting non-Hodgkin's lymphoma (NHL), Her-2/neu highly expressing metastatic breast cancer, colorectal cancer, acute myelogenous leukemia, and B-cell chronic lymphocytic leukemia (CLL) have received FDA approval. Promising new targets for antibody therapy include cellular growth factor receptors, mediators of tumor-driven neo-angiogenesis, as well as host negative immunoregulatory checkpoints that impede an effective immune response to neoplasia. Antibody efficacy has been increased by genetic engineering to humanize the antibodies and to increase their effector functions including antibody dependent cellular cytotoxicity. Furthermore, antibodies have been armed with cytokines, chemotherapeutic agents, toxins, and radionuclides to augment their efficacy as tumor cytotoxic agents. As a consequence of these advances, 30 years after their first development, monoclonal antibodies have become an important standard approach for the therapy of neoplasia with 19 therapeutic monoclonal antibodies now approved by the FDA including 8 for the treatment of cancer.