The CD20 gene encodes a protein expressed on the membrane of B cells: it appears on the surface of normal and malignant B lymphocytes during the pre-B-cell stage. Due to this expression, it has become an interesting target for therapy in CD20-positive B-cell malignancies. Since the introduction of the first-in-class anti-CD20 monoclonal antibody (mAb) rituximab, targeted anti-CD20 mAbs therapy has become the main-stay in the treatment of non-Hodgkin’s lymphomas (NHL), and rituximab-based therapies are among the most commonly used treatments. Moreover, rituximab paved the way for other engineered antibodies, namely obinutuzumab and ofatumumab. Lately, the recent introduction of CD20xCD3 bispecific anti- bodies (BsAbs), an innovative immunotherapeutic approach that redirects endogenous CD3-positive T-cells to recognize CD20-positive tumor cells, has shown very promising efficacy in lymphoma treatment. Similarly, although historically anti-CD19 oriented, chimeric antigen receptor (CAR)-T cell therapy has also been introduced as a novel anti-CD20 therapy. Since the introduction of mAbs, several mechanisms have been identified as potentially involved in anti-CD20 resistance, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), loss of CD20, and induction of apoptosis. More recent studies suggest that tumor microenvironment could also be implicated. This chapter discusses the clinical applications of the three main anti-CD20 mAbs (rituximab, obinutuzumab, and ofatumumab) nowadays and briefly touches on the current experience with anti-CD20xCD3 BsAbs. Subsequently, known mechanisms of resistance to anti-CD20 therapy will be described, concluding with some considerations on future perspectives.
Non-Hodgkin lymphoma treated with anti-CD20 antibody-based immunochemotherapy
Michele Clerico;Simone Ragaini;Cavallo Federica
2023-01-01
Abstract
The CD20 gene encodes a protein expressed on the membrane of B cells: it appears on the surface of normal and malignant B lymphocytes during the pre-B-cell stage. Due to this expression, it has become an interesting target for therapy in CD20-positive B-cell malignancies. Since the introduction of the first-in-class anti-CD20 monoclonal antibody (mAb) rituximab, targeted anti-CD20 mAbs therapy has become the main-stay in the treatment of non-Hodgkin’s lymphomas (NHL), and rituximab-based therapies are among the most commonly used treatments. Moreover, rituximab paved the way for other engineered antibodies, namely obinutuzumab and ofatumumab. Lately, the recent introduction of CD20xCD3 bispecific anti- bodies (BsAbs), an innovative immunotherapeutic approach that redirects endogenous CD3-positive T-cells to recognize CD20-positive tumor cells, has shown very promising efficacy in lymphoma treatment. Similarly, although historically anti-CD19 oriented, chimeric antigen receptor (CAR)-T cell therapy has also been introduced as a novel anti-CD20 therapy. Since the introduction of mAbs, several mechanisms have been identified as potentially involved in anti-CD20 resistance, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), loss of CD20, and induction of apoptosis. More recent studies suggest that tumor microenvironment could also be implicated. This chapter discusses the clinical applications of the three main anti-CD20 mAbs (rituximab, obinutuzumab, and ofatumumab) nowadays and briefly touches on the current experience with anti-CD20xCD3 BsAbs. Subsequently, known mechanisms of resistance to anti-CD20 therapy will be described, concluding with some considerations on future perspectives.
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