Antibody-based therapeutics for the treatment of human B cell malignancies

The dynamic expression of various phenotypic markers during B cell development not only defines the particular stage in ontogeny but also provides the necessary growth, differentiation, maturation and survival signals. When a B cell at any given stage becomes cancerous, these cell surface molecules, intracellular signaling molecules, and the over-expressed gene products become favorite targets for potential therapeutic intervention. Various adaptive and adoptive immunotherapeutic approaches induce T cell and antibody responses against cancer cells, and successful remission leading to minimal residual disease has been obtained. Nonetheless, subsequent relapse and development of resistant clones prompted further development and several novel strategies are evolving. Engineered monoclonal antibodies with high affinity and specificity to target antigens have been developed and used either alone or in combination with chemotherapeutic drugs. They are also used as vehicles to deliver cytotoxic drugs, toxins, or radionuclides that are either directly conjugated or encapsulated in liposomal vesicles. Likewise, genetically engineered T cells bearing chimeric antigen receptors are used to redirect cytotoxicity to antigen-positive target cells. This review describes recent advancements in some of these adoptive immunotherapeutic strategies targeting B cell malignancies.