Targeting CD20: teaching an old dog new tricks

Abstract

Rituximab was the first monoclonal antibody used for the treatment of a malignancy. In the 22 years since initial approval, it has become a vital component of therapy for a multitude of B-cell malignancies. Within the last several years, however, there has been a robust development of novel agents targeting CD20, including second generation anti-CD20 antibodies, biosimilar antibodies, and subcutaneous formulations that have been approved. The era of passive immunotherapy is now yielding to therapeutic approaches that actively engage the immune system. Emerging approaches leverage immunomodulatory drugs or novel checkpoint inhibitors to enhance CD20 therapy. Recent data sets on bispecific CD3/CD20 antibodies demonstrate exciting early findings, and CD20-directed chimeric antigen receptor T-cell therapies are now entering clinical trials. Anti-CD20 therapies are a vital component of the treatment of B-cell malignancies, and there is a dynamic therapeutic environment with multiple new data sets reviewed here.

Monoclonal antibodies used for management of hematological disorders

“…The area is ever expanding and with biosimilars, conjugates, engineered antibodies and with repurposing of the antibodies for many other conditions than the original ones for which the product was discovered makes this field of hemotherapeutics a rapidly progressive area. [71,[79][80] Monoclonal antibodies (MAs) produce a different set of side effects compared to many other types of drugs used in hematology. Hence, they can be combined with various other types of therapies with significant improvement in outcome without increase in one type of side effects.…”

“…Crizanlizumab (Adakveo R ): This humanized monoclonal antibody (MA) is directed towards P selectin on endothelial cells and has been successfully employed to treat vasoocclusive crisis in Sickle cell disease for which FDA has approved the product. [79,80] It has also been tested with Ruxolitinib for idiopathic myelofibrosis. [61].…”

Targeted Agents in the Treatment of Indolent B-Cell Non-Hodgkin Lymphomas

“…CD20 is present on mature B-cells and most malignant B-lymphocytes and was the target for the first approved monoclonal antibody, rituximab, for use in malignancy [ 146 ]. Rituximab is a type I mAb targeting CD20 that induces both complement dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).…”

Targeting Bruton’s Tyrosine Kinase in CLL

“…The newer generation of anti-CD20 mAbs exhibits improved effector function compared to rituximab and has been shown to circumvent mechanisms of rituximab failure in vitro . Obinutuzumab, a glycoengineered type 2 antibody, induces greater direct cell killing, greater antibody-dependent cellular cytotoxicity (ADCC), and less intra- and trans-cellular loss of target antigens compared to rituximab ( 71 ). Ublituximab is a glycoengineered type 1 antibody that targets a unique epitope of CD20 and has shown greater ADCC than rituximab in vitro ( 72 ).…”