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.