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Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?

Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) are used to block cell-s...

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Autores principales: Jalalizadeh, Mehrsa, Yadollahvandmiandoab, Reza, Reis, Leonardo Oliveira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857673/
https://www.ncbi.nlm.nih.gov/pubmed/36661747
http://dx.doi.org/10.3390/curroncol30010098
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author Jalalizadeh, Mehrsa
Yadollahvandmiandoab, Reza
Reis, Leonardo Oliveira
author_facet Jalalizadeh, Mehrsa
Yadollahvandmiandoab, Reza
Reis, Leonardo Oliveira
author_sort Jalalizadeh, Mehrsa
collection PubMed
description Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) are used to block cell-surface glycoproteins responsible for cancer immune escape. However, only a subset of patients benefit from this treatment. In this commentary, we focus on the polymorphism in the target molecules of these mAbs, namely PD-1, PD-L1 and CTLA4; we explain that using a single mAb from one clone is unlikely to succeed in treating all humans because humans have a genotype and phenotype polymorphism in these molecules. Monoclonal antibodies are highly specific and are capable of recognizing only one epitope (“monospecific”), which makes them ideal for use in laboratory animals because these animals are generationally inbred and genetically identical (isogenic). In humans, however, the encoding genes for PD-1, PD-L1 and CTLA4 have variations (alleles), and the final protein products have phenotype polymorphism. This means that small differences exist in these proteins among individual humans, rendering one mAb too specific to cover all patients. Our suggestion for the next step in advancing this oncotherapy is to focus on methods to tailor the mAb treatment individually for each patient or replace a single clone of mAb with less specific alternatives, e.g., a “cocktail of mAbs”, oligoclonal antibodies or recombinant polyclonal antibodies. Fortunately, there are ongoing clinical trials on oligoclonal antibodies at the moment.
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spelling pubmed-98576732023-01-21 Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific? Jalalizadeh, Mehrsa Yadollahvandmiandoab, Reza Reis, Leonardo Oliveira Curr Oncol Commentary Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) are used to block cell-surface glycoproteins responsible for cancer immune escape. However, only a subset of patients benefit from this treatment. In this commentary, we focus on the polymorphism in the target molecules of these mAbs, namely PD-1, PD-L1 and CTLA4; we explain that using a single mAb from one clone is unlikely to succeed in treating all humans because humans have a genotype and phenotype polymorphism in these molecules. Monoclonal antibodies are highly specific and are capable of recognizing only one epitope (“monospecific”), which makes them ideal for use in laboratory animals because these animals are generationally inbred and genetically identical (isogenic). In humans, however, the encoding genes for PD-1, PD-L1 and CTLA4 have variations (alleles), and the final protein products have phenotype polymorphism. This means that small differences exist in these proteins among individual humans, rendering one mAb too specific to cover all patients. Our suggestion for the next step in advancing this oncotherapy is to focus on methods to tailor the mAb treatment individually for each patient or replace a single clone of mAb with less specific alternatives, e.g., a “cocktail of mAbs”, oligoclonal antibodies or recombinant polyclonal antibodies. Fortunately, there are ongoing clinical trials on oligoclonal antibodies at the moment. MDPI 2023-01-16 /pmc/articles/PMC9857673/ /pubmed/36661747 http://dx.doi.org/10.3390/curroncol30010098 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Commentary
Jalalizadeh, Mehrsa
Yadollahvandmiandoab, Reza
Reis, Leonardo Oliveira
Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title_full Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title_fullStr Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title_full_unstemmed Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title_short Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
title_sort immune checkpoint glycoproteins have polymorphism: are monoclonal antibodies too specific?
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857673/
https://www.ncbi.nlm.nih.gov/pubmed/36661747
http://dx.doi.org/10.3390/curroncol30010098
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