Jacobs Journal of Cancer Science and Research

Mechanisms of Resistance to Rituximab in B-cell Lymphoma

*Timothy Allen
Department Of Oncology, Center For Excellence In Research And Development, United States

*Corresponding Author:
Timothy Allen
Department Of Oncology, Center For Excellence In Research And Development, United States
Email:Timothy.Allen@gapsos.com

Published on: 2015-03-14

Abstract

Rituximab or Anti-CD20, is a chimeric monoclonal antibody (MoAb)that has become a ubiquitous component for improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL)and other known hematological malignancies. The MoAbs has the direct antiproliferative effect on the B cells in vitro. This review article focuses on the mechanism of resistance to the Rituximab(anti CD-20)mediated cytotoxicity.Understanding of the complexity of mechanism facilitates the progressof pharmacological strategies to reduce resistance.Unluckily, the common responses to single-agent Rituximab are inadequate, It has multiple mechanisms which commonly includes antibody-dependent cell- mediated cytotoxicity and complement- dependent cytotoxicity. Tumor/host -associated factors contribute to the Rituximab resistance. There are many approaches to overcome rituximab resistance such as engineered antibodies, radio-immunoconjugates and rational biologic combination immunotherapy, which provide a comprehensive understanding of interactions between its multiple mechanisms of action.Furthermore, few discussed studies in this review show that treatment with rituximab can be modified and may have a significant role in newer therapeutical strategies.

Keywords

B-cell non-Hodgkin Lymphoma (B-NHL); Antibody Dependent Cell Mediated Cytotoxicity (ADCC); Complement Dependent Cytotoxicity (CDC); Anti-CD20, Monoclonal-Antibody; B-cell depletion

Introduction

Based on the safety and efficacy data,rituximab, a chimeric monoclonal antibody was approved by USFDA on 26 November1997 for the treatment of non-Hodgkin lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Rheumatoid Arthritis (RA) and Granulomatosis with Polyangiitis (GPA)(Wegener’sGranulomatosis) and Microscopic Polyangiitis (MPA). For NHL, rituximab can be used alone or in combination with other chemotherapy medicine. It is the recombinant DNA technology made IgG1 kappa antibody targeting the CD20 antigen, which is usually found on malignant or normal B lymphocytes. It has molecular weight of approximately 145kD with binding affity of approximately 8.0 nM towards CD20 antigen. Antibody Isotype IgG1 (Immunoglobin G) contains light and heavy variable chain sequence. Rituximib is composed of 213 amino acids, in lightchain and 451 amino acids in the heavy chain. It is produced by mammalian cell (Chinese Hamster Ovary) suspension culture in a nutrient medium containing the antibiotic gentamicin. Non- Hodgkin lymphoma (NHL) is a cancer of the B lymphocytes. Bone marrow, spleen, thymus, adenoids and tonsils, digestive tract and lymph nodes are the major sites of lymphoid tissues which have more chances to develop lymphomas.