A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections

Seyfizadeh, Nayer; Hasenkamp, Justin; Huerta-Yépez, Sara

doi:10.1016/j.critrevonc.2015.09.001

Cited by 72 publications

(61 citation statements)

References 198 publications

(197 reference statements)

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“…They generate cytokines, activate T cells and can act as antigen-presenting cells [5]. The CD20 receptor is found on the cell surface of B-cells at their pre-B-cell stage [6]. It is not expressed on other tissues and does not appear on B-cells after their differentiation into plasma cells [5].…”

Section: Introductionmentioning

confidence: 99%

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Infectious complications of rituximab therapy in renal disease

Nixon

Ogden²,

Woywodt

et al. 2017

Clinical Kidney Journal

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Rituximab, an anti-CD20 monoclonal antibody, was originally used to treat B-cell malignancies. Its use has significantly increased in recent years, as it is now also used to treat a variety of autoimmune diseases including rheumatoid arthritis and ANCA-associated vasculitis (AAV). Initial studies suggested that the adverse effects of rituximab were minimal. Though the risk of malignancy with rituximab-based immunosuppressive regimens appears similar to that of the general population, there are now concerns regarding the risk of infectious complications. Rituximab has been associated with serious infections, including Pneumocystis jiroveci pneumonia (PJP) and the reactivation of hepatitis B virus (HBV) and tuberculosis (TB). The risk of infection appears to be the result of a variety of mechanisms, including prolonged B-cell depletion, B-cell–T-cell crosstalk, panhypogammaglobulinaemia, late-onset neutropenia and blunting of the immune response after vaccination. Importantly, the risk of infectious complications is also related to individual patient characteristics and the indication for rituximab. Individualization of treatment is, therefore, crucial. Particular attention should be given to strategies to minimize the risk of infectious complications, including vaccinating against bacterial and viral pathogens, monitoring white cell count and immunoglobulin levels, prophylaxis against PJP and screening for HBV and TB.

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Section: Introductionmentioning

confidence: 99%

“…It is not expressed on other tissues and does not appear on B-cells after their differentiation into plasma cells [5]. Rituximab targets the CD20 receptor leading to B-cell depletion through complement-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and B-cell apoptosis [6]. …”

Section: Introductionmentioning

confidence: 99%

Infectious complications of rituximab therapy in renal disease

Nixon

Ogden²,

Woywodt

et al. 2017

Clinical Kidney Journal

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“…Then CD20 recycled back to the surface and left RTX consumed in the lysosome. 4,9 Meanwhile, the recovery of surface CD20 was slow and incomplete after P-(MORF2) 10 was added to Fab′-MORF1 pretargeted cells. As it is generally accepted that efficient receptor cross-linking induces receptor endocytosis into lysosomes 28 and multivalent P-(MORF2) x effector could bind multiple Fab′-MORF1 engagers on the cell surface as guaranteed by the lack of Fc-Fc γ receptor interaction, this strengthened hyper-cross-linking was expected to trigger CD20 endocytosis and redirected CD20 from the recycling pathway primarily to the internalization pathway.…”

Section: Resultsmentioning

confidence: 99%

“…3 The immunotherapy using anti-CD20 monoclonal antibody rituximab (RTX) is the current standard of care alongside conventional chemotherapy. 4 However, while <10% of NHL patients receiving RTX-based therapy show complete remission, the relapsed and refractory disease continue to constitute major challenges. 5 …”

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confidence: 99%

Amplification of CD20 Cross-Linking in Rituximab-Resistant B-Lymphoma Cells Enhances Apoptosis Induction by Drug-Free Macromolecular Therapeutics

Yang

Wang

et al. 2018

ACS Nano

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Although the CD20-targeted monoclonal antibody rituximab (RTX) has revolutionized the therapeutic landscape for B-cell malignancy, relapsed and refractory disease due to RTX resistance continue to constitute major challenges, illustrating the need for better therapies. Here, we apply drug-free macromolecular therapeutics (DFMT) that amplifies CD20 cross-linking to enhance apoptosis in RTX-resistant cells. Bispecific engager (anti-CD20 Fab′ conjugated with oligonucleotide1) pretargets CD20 and the deletion of Fc-region minimizes its premature endocytosis in resistant cells that rapidly internalize and consume CD20/RTX complexes. Second-step delivery of multivalent polymeric effector (linear copolymer conjugated with multiple copies of complementary oligonucleotide 2) simultaneously hybridizes multiple CD20-bound engagers and strengthens CD20 ligation. Moreover, the restoration of CD20 expression by the pretreatment of cells with a polymer-gemcitabine conjugate, a CD20 expression enhancer, unleashes the full potential of DFMT in the CD20-deficient resistant cells. Hence, amplification of CD20 cross-linking is achieved by (1) the enhancement of surface CD20 accessibility, (2) the increase in CD20 expression, and (3) multimeric CD20 binding, which ultimately translates into the amplified activation of a wide range of innate apoptotic responses. We demonstrated that the altered molecular signaling pathway that originally results in RTX resistance could be circumvented and compensated by other DFMT-augmented pathways. Of note, our preliminary data provide proof-of-concept that CD20 cross-linking amplification emerges as an important strategy for overcoming RTX resistance.

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“…Детальная характеристика меха-низмов действия РТМ и последствий «депле-ции» В-клеток при РА детально обсуждены в наших предыдущих публикациях [10,12], обзорах других авторов [13,14]. Эффектив-ность и безопасность РТМ как у пациентов с развернутым РА, резистентных к базисным противовоспалительным препаратам (БПВП) и ингибиторам ФНОα, так и у пациентов с ранним РА в качестве «первого» генно-ин-женерного биологического препарата (ГИБП) подтверждена в многочисленных широкомасштабных рандомизированных плацебоконтролируемых исследованиях (РПКИ), материалы которых суммированы в обзорах [10][11][12], их метаанализах [15][16][17], а также данными реальной клинической пра-ктики в рамках наблюдательных исследова-ний и национальных регистров [18][19][20][21].…”

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The Efficacy and Safety of Rituximab Biosimilar (Acellbia®) in Rheumatoid Arthritis as the First Biological Agent: Results of Phase Iii (Alterra) Clinical Trial

Nasonov

Мазуров

Зонова

et al. 2017

Naučno-praktičeskaâ revmatologiâ

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The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p<0.0001). The differences in the ACR20 response rate in the two groups were 36.3% (95% CI, 19.27–53.28%). There were significant differences between the groups in the ACR50 response rates: 28.4% and 5.9% (p=0.001) and in the ACR70 ones: 12.8% and only 2.0%, respectively (p=0.036). Analysis of all recorded adverse events (AE) frequency showed no significant differences between the patients in the study and control groups and demonstrates its equivalence with that of RTM (MabThera®); all the AE were expectable. It is noted that antibodies to RTM with binding and neutralizing activities had no impact on the efficiency and safety of therapy.

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A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections

Cited by 72 publications

References 198 publications

Infectious complications of rituximab therapy in renal disease

Infectious complications of rituximab therapy in renal disease

Amplification of CD20 Cross-Linking in Rituximab-Resistant B-Lymphoma Cells Enhances Apoptosis Induction by Drug-Free Macromolecular Therapeutics

The Efficacy and Safety of Rituximab Biosimilar (Acellbia®) in Rheumatoid Arthritis as the First Biological Agent: Results of Phase Iii (Alterra) Clinical Trial

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