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Fulltext SARS-CoV-2 neutralizing antibody bebtelovimab - a systematic scoping review and meta-analysis

Liew MNY, Kua KP, Lee SWH, Wong KK

Front Immunol, 2023;14:1100263.
PMID: 37701439 DOI: 10.3389/fimmu.2023.1100263

INTRODUCTION: The COVID-19 pandemic is a major global public health crisis. More than 2 years into the pandemic, effective therapeutic options remain limited due to rapid viral evolution. Stemming from the emergence of multiple variants, several monoclonal antibodies are no longer suitable for clinical use. This scoping review aimed to summarize the preclinical and clinical evidence for bebtelovimab in treating newly emerging SARS-CoV-2 variants.
METHODS: We systematically searched five electronic databases (PubMed, CENTRAL, Embase, Global Health, and PsycINFO) from date of inception to September 30, 2022, for studies reporting on the effect of bebtelovimab in SARS-CoV-2 infection, using a combination of search terms around -bebtelovimab‖, -LY-CoV1404‖, -LY3853113‖, and -coronavirus infection‖. All citations were screened independently by two researchers. Data were extracted and thematically analyzed based on study design by adhering to the stipulated scoping review approaches.
RESULTS: Thirty-nine studies were included, thirty-four non-clinical studies were narratively synthesized, and five clinical studies were meta-analyzed. The non-clinical studies revealed bebtelovimab not only potently neutralized wide-type SARS-CoV-2 and existing variants of concern such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but also retained appreciable activity against Omicron lineages, including BA.2.75, BA.4, BA.4.6, and BA.5. Unlike other monoclonal antibodies, bebtelovimab was able to bind to epitope of the SARS-CoV-2 S protein by exploiting loop mobility or by minimizing side-chain interactions. Pooled analysis from clinical studies depicted that the rates of hospitalization, ICU admission, and death were similar between bebtelovimab and other COVID-19 therapies. Bebtelovimab was associated with a low incidence of treatment-emergent adverse events.
CONCLUSION: Preclinical evidence suggests bebtelovimab be a potential treatment for COVID-19 amidst viral evolution. Bebtelovimab has comparable efficacy to other COVID-19 therapies without evident safety concerns.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects
Computer-Aided Antibody Design: An Overview

Choong YS, Lee YV, Soong JX, Law CT, Lim YY

Adv Exp Med Biol, 2017;1053:221-243.
PMID: 29549642 DOI: 10.1007/978-3-319-72077-7_11

The use of monoclonal antibody as the next generation protein therapeutics with remarkable success has surged the development of antibody engineering to design molecules for optimizing affinity, better efficacy, greater safety and therapeutic function. Therefore, computational methods have become increasingly important to generate hypotheses, interpret and guide experimental works. In this chapter, we discussed the overall antibody design by computational approches.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects
A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease

Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.

COPD, 2017 Oct;14(5):476-483.
PMID: 28753067 DOI: 10.1080/15412555.2017.1335697

Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects
Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):30-36.
PMID: 29024102 DOI: 10.1111/jgh.14018

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects
Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment

Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.

J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
PMID: 29023903 DOI: 10.1111/jgh.14019

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects
Counterpoint. Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine

Bhattachary-Chatterjee M, Nath Baral R, Chatterjee SK, Das R, Zeytin H, Chakraborty M, et al.

Cancer Immunol Immunother, 2000 Jun;49(3):133-41.
PMID: 10881692

Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.

Matched MeSH terms: Antibodies, Monoclonal/adverse effects