Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy

Esteban Cruz, Veysel KayserSchool of Pharmacy, The University of Sydney, Sydney, NSW, AustraliaAbstract: Monoclonal antibodies (mAbs) have become a cornerstone in the therapeutic guidelines of a wide range of solid tumors. The targeted nature of these biotherapeutics has improved treatment outcomes...

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Autores principales:	Cruz E, Kayser V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	antibody therapy treatment resistance antibody-drug conjugates immune checkpoint inhibitors nanoparticle delivery vehicles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/47df797738d34ba48a6a75b530a77069
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spelling	oai:doaj.org-article:47df797738d34ba48a6a75b530a770692021-12-02T13:15:15ZMonoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy1177-5491https://doaj.org/article/47df797738d34ba48a6a75b530a770692019-05-01T00:00:00Zhttps://www.dovepress.com/monoclonal-antibody-therapy-of-solid-tumors-clinical-limitations-and-n-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491Esteban Cruz, Veysel KayserSchool of Pharmacy, The University of Sydney, Sydney, NSW, AustraliaAbstract: Monoclonal antibodies (mAbs) have become a cornerstone in the therapeutic guidelines of a wide range of solid tumors. The targeted nature of these biotherapeutics has improved treatment outcomes by offering enhanced specificity to reduce severe side effects experienced with conventional chemotherapy. Notwithstanding, poor tumor tissue penetration and the heterogeneous distribution achieved therein are prominent drawbacks that hamper the clinical efficacy of therapeutic antibodies. Failure to deliver efficacious doses throughout the tumor can lead to treatment failure and the development of acquired resistance mechanisms. Comprehending the morphological and physiological characteristics of solid tumors and their microenvironment that affect tumor penetration and distribution is a key requirement to improve clinical outcomes and realize the full potential of monoclonal antibodies in oncology. This review summarizes the essential architectural characteristics of solid tumors that obstruct macromolecule penetration into the targeted tissue following systemic delivery. It further describes mechanisms of resistance elucidated for blockbuster antibodies for which extensive clinical data exists, as a way to illustrate various modes in which cancer cells can overcome the anticancer activity of therapeutic antibodies. Thereafter, it describes novel strategies designed to improve clinical outcomes of mAbs by increasing potency and/or improving tumor delivery; focusing on the recent clinical success and growing clinical pipeline of antibody-drug conjugates, immune checkpoint inhibitors and nanoparticle-based delivery systems.Keywords: antibody therapy, treatment resistance, antibody–drug conjugates, immune checkpoint inhibitors, nanoparticle delivery vehiclesCruz EKayser VDove Medical Pressarticleantibody therapytreatment resistanceantibody-drug conjugatesimmune checkpoint inhibitorsnanoparticle delivery vehiclesMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 13, Pp 33-51 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody therapy treatment resistance antibody-drug conjugates immune checkpoint inhibitors nanoparticle delivery vehicles Medicine (General) R5-920
spellingShingle	antibody therapy treatment resistance antibody-drug conjugates immune checkpoint inhibitors nanoparticle delivery vehicles Medicine (General) R5-920 Cruz E Kayser V Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
description	Esteban Cruz, Veysel KayserSchool of Pharmacy, The University of Sydney, Sydney, NSW, AustraliaAbstract: Monoclonal antibodies (mAbs) have become a cornerstone in the therapeutic guidelines of a wide range of solid tumors. The targeted nature of these biotherapeutics has improved treatment outcomes by offering enhanced specificity to reduce severe side effects experienced with conventional chemotherapy. Notwithstanding, poor tumor tissue penetration and the heterogeneous distribution achieved therein are prominent drawbacks that hamper the clinical efficacy of therapeutic antibodies. Failure to deliver efficacious doses throughout the tumor can lead to treatment failure and the development of acquired resistance mechanisms. Comprehending the morphological and physiological characteristics of solid tumors and their microenvironment that affect tumor penetration and distribution is a key requirement to improve clinical outcomes and realize the full potential of monoclonal antibodies in oncology. This review summarizes the essential architectural characteristics of solid tumors that obstruct macromolecule penetration into the targeted tissue following systemic delivery. It further describes mechanisms of resistance elucidated for blockbuster antibodies for which extensive clinical data exists, as a way to illustrate various modes in which cancer cells can overcome the anticancer activity of therapeutic antibodies. Thereafter, it describes novel strategies designed to improve clinical outcomes of mAbs by increasing potency and/or improving tumor delivery; focusing on the recent clinical success and growing clinical pipeline of antibody-drug conjugates, immune checkpoint inhibitors and nanoparticle-based delivery systems.Keywords: antibody therapy, treatment resistance, antibody–drug conjugates, immune checkpoint inhibitors, nanoparticle delivery vehicles
format	article
author	Cruz E Kayser V
author_facet	Cruz E Kayser V
author_sort	Cruz E
title	Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
title_short	Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
title_full	Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
title_fullStr	Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
title_full_unstemmed	Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
title_sort	monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/47df797738d34ba48a6a75b530a77069
work_keys_str_mv	AT cruze monoclonalantibodytherapyofsolidtumorsclinicallimitationsandnovelstrategiestoenhancetreatmentefficacy AT kayserv monoclonalantibodytherapyofsolidtumorsclinicallimitationsandnovelstrategiestoenhancetreatmentefficacy
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Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy

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