Development of Anti-CD20 Antigen-Targeting Therapies for B-cell Lymphoproliferative Malignancies - The State of the Art.

For decades, the available anticancer therapies were mostly based on nonspecific cytotoxic regimens. These cytostatic combinations, while effective in some subpopulations of patients, are often limited by extensive toxicity and/or development of tumor resistance. Although standard chemotherapy still remains a common therapeutic tool in the fight with cancer, immunotherapy increasingly revolutionizes treatment strategy for several hematologic malignancies. For a subset of patients with B-cell lymphoproliferative disease, the introduction of subsequently developed classes of anti-CD20 monoclonal antibodies (mAbs) has resulted in improved overall response rates and, to some extent, patient overall survival. Rituximab, the most thoroughly-explored chimeric mouse anti-human anti-CD20 mAb, has been widely and successfully introduced to oncohematology, but also to other fields of medicine, such as transfusiology or rheumatology. Currently, several new generation anti-CD20 mAbs are undergoing different stages of preclinical and clinical studies of assessment to further improve the outcome and overcome mechanisms of resistance. The nature of the direct mechanisms responsible for the anticancer properties of different classes of anti-CD20 mAbs is still not fully understood. This is reflected in different approaches during the investigation of novel anti-CD20 agents. So far, three classes of anti- CD20 mAb have been described. In this review, we focus on CD20 antigen-targeting therapies both currently available and undergoing preclinical or clinical investigation for B-cell lymphoproliferative malignancies.