Monoclonal antibodies for prevention or treatment of HIV-1 infection: what next after the first clinical trials?

Virologie ◽  
2021 ◽  
Vol 25 (6) ◽  
pp. 291-300
Author(s):  
Karl Stefic ◽  
Francis Barin
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Hiv 1

scholarly journals Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs

2015 ◽  
Vol 90 (3) ◽  
pp. 1321-1332 ◽  
Author(s):  
Diane L. Bolton ◽  
Amarendra Pegu ◽  
Keyun Wang ◽  
Kathleen McGinnis ◽  
Martha Nason ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Antiretroviral Therapy ◽  
Envelope Glycoprotein ◽  
Plasma Viremia ◽  
Immunodeficiency Virus ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTCombination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection.IMPORTANCETreatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of MAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.

Antibody Therapy for the Control of Viral Diseases: An Update

2019 ◽  
Vol 20 (13) ◽  
pp. 1108-1121 ◽  
Author(s):  
Miriam Dibo ◽  
Eduardo C. Battocchio ◽  
Lucas M. dos Santos Souza ◽  
Matheus D. Veloso da Silva ◽  
Bruna K. Banin-Hirata ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Viral Antigen ◽  
Viral Infections ◽  
Antibody Therapy ◽  
Therapeutic Strategies ◽  
Viral Diseases ◽  
Specific Antibodies ◽  
The Status ◽  
Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

scholarly journals Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 34 ◽  
Author(s):  
Ahmad Iftikhar ◽  
Hamza Hassan ◽  
Nimra Iftikhar ◽  
Adeela Mushtaq ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Combination Therapy ◽  
Immune Responses ◽  
Web Of Science ◽  
Cochrane Library ◽  
Future Perspectives ◽  
Antibody Drug Conjugate ◽  
Chemotherapy Agents

Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively. Conclusions: Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted.

scholarly journals Structure-function relationships of HIV-1 reverse transcriptase determined using monoclonal antibodies.

1992 ◽  
Vol 267 (21) ◽  
pp. 14654-14661
Author(s):  
T Restle ◽  
M Pawlita ◽  
G Sczakiel ◽  
B Müller ◽  
R.S. Goody
Keyword(s):  
Monoclonal Antibodies ◽  
Reverse Transcriptase ◽  
Structure Function ◽  
Hiv 1

scholarly journals Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling

Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 40
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Prediction Error ◽  
Allometric Scaling ◽  
Polyclonal Antibodies ◽  
Therapeutic Proteins ◽  
Preterm Neonates ◽  
Pharmacokinetic Parameters ◽  
Pediatric Dose ◽  
Age Dependent

Allometric scaling can be used for the extrapolation of pharmacokinetic parameters from adults to children. The objective of this study was to predict clearance of therapeutic proteins (monoclonal and polyclonal antibodies and non-antibody proteins) allometrically in preterm neonates to adolescents. There were 13 monoclonal antibodies, seven polyclonal antibodies, and nine therapeutic proteins (non-antibodies) in the study. The clearance of therapeutic proteins was predicted using the age dependent exponents (ADE) model and then compared with the observed clearance values. There were in total 29 therapeutic proteins in this study with 75 observations. The number of observations with ≤30%, ≤50%, and >50% prediction error was 60 (80%), 72 (96%), and 3 (4%), respectively. Overall, the predicted clearance values of therapeutic proteins in children was good. The allometric method proposed in this manuscript can be used to select first-in-pediatric dose of therapeutic proteins in pediatric clinical trials.

Analyzing Plasma HIV-1 RNA Measurements as Multiple Recurrent Events in Clinical Trials

2006 ◽  
Vol 7 (3) ◽  
pp. 116-124 ◽  
Author(s):  
Philippe Flandre ◽  
Claire Pinçon ◽  
Jean-Pierre Aboulker ◽  
Françoise Brun-Vézinet ◽  
Gilles Pialoux ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Recurrent Events ◽  
Hiv 1
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