Cargando…

The Current Landscape of Antibody-based Therapies in Solid Malignancies

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats w...

Descripción completa

Detalles Bibliográficos
Autores principales: Shah, Ashu, Rauth, Sanchita, Aithal, Abhijit, Kaur, Sukhwinder, Ganguly, Koelina, Orzechowski, Catherine, Varshney, Grish C, Jain, Maneesh, Batra, Surinder K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738893/
https://www.ncbi.nlm.nih.gov/pubmed/33391547
http://dx.doi.org/10.7150/thno.52614
_version_ 1783623220134412288
author Shah, Ashu
Rauth, Sanchita
Aithal, Abhijit
Kaur, Sukhwinder
Ganguly, Koelina
Orzechowski, Catherine
Varshney, Grish C
Jain, Maneesh
Batra, Surinder K
author_facet Shah, Ashu
Rauth, Sanchita
Aithal, Abhijit
Kaur, Sukhwinder
Ganguly, Koelina
Orzechowski, Catherine
Varshney, Grish C
Jain, Maneesh
Batra, Surinder K
author_sort Shah, Ashu
collection PubMed
description Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance that is not only caused by the heterogeneity of tumor antigen, but also the resistance imposed by tumor microenvironment (TME), including inefficient delivery to the tumor, alteration of effector functions in the TME, and Fc-gamma receptor expression diversity and polymorphism. Further, this article provides a perspective on potential strategies to overcome these barriers and how diagnostic and prognostic biomarkers are being used in predicting response to mAb-based therapies. Overall, understanding these interdependent parameters can improve the current mAb-based formulations and develop novel mAb-based therapeutics for achieving durable clinical outcomes in a large subset of patients.
format Online
Article
Text
id pubmed-7738893
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-77388932021-01-01 The Current Landscape of Antibody-based Therapies in Solid Malignancies Shah, Ashu Rauth, Sanchita Aithal, Abhijit Kaur, Sukhwinder Ganguly, Koelina Orzechowski, Catherine Varshney, Grish C Jain, Maneesh Batra, Surinder K Theranostics Review Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance that is not only caused by the heterogeneity of tumor antigen, but also the resistance imposed by tumor microenvironment (TME), including inefficient delivery to the tumor, alteration of effector functions in the TME, and Fc-gamma receptor expression diversity and polymorphism. Further, this article provides a perspective on potential strategies to overcome these barriers and how diagnostic and prognostic biomarkers are being used in predicting response to mAb-based therapies. Overall, understanding these interdependent parameters can improve the current mAb-based formulations and develop novel mAb-based therapeutics for achieving durable clinical outcomes in a large subset of patients. Ivyspring International Publisher 2021-01-01 /pmc/articles/PMC7738893/ /pubmed/33391547 http://dx.doi.org/10.7150/thno.52614 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Review
Shah, Ashu
Rauth, Sanchita
Aithal, Abhijit
Kaur, Sukhwinder
Ganguly, Koelina
Orzechowski, Catherine
Varshney, Grish C
Jain, Maneesh
Batra, Surinder K
The Current Landscape of Antibody-based Therapies in Solid Malignancies
title The Current Landscape of Antibody-based Therapies in Solid Malignancies
title_full The Current Landscape of Antibody-based Therapies in Solid Malignancies
title_fullStr The Current Landscape of Antibody-based Therapies in Solid Malignancies
title_full_unstemmed The Current Landscape of Antibody-based Therapies in Solid Malignancies
title_short The Current Landscape of Antibody-based Therapies in Solid Malignancies
title_sort current landscape of antibody-based therapies in solid malignancies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738893/
https://www.ncbi.nlm.nih.gov/pubmed/33391547
http://dx.doi.org/10.7150/thno.52614
work_keys_str_mv AT shahashu thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT rauthsanchita thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT aithalabhijit thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT kaursukhwinder thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT gangulykoelina thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT orzechowskicatherine thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT varshneygrishc thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT jainmaneesh thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT batrasurinderk thecurrentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT shahashu currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT rauthsanchita currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT aithalabhijit currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT kaursukhwinder currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT gangulykoelina currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT orzechowskicatherine currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT varshneygrishc currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT jainmaneesh currentlandscapeofantibodybasedtherapiesinsolidmalignancies
AT batrasurinderk currentlandscapeofantibodybasedtherapiesinsolidmalignancies