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The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promot...

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Detalles Bibliográficos
Autores principales: Nelson, Delia, Fisher, Scott, Robinson, Bruce
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052171/
https://www.ncbi.nlm.nih.gov/pubmed/24955376
http://dx.doi.org/10.1155/2014/789069
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author Nelson, Delia
Fisher, Scott
Robinson, Bruce
author_facet Nelson, Delia
Fisher, Scott
Robinson, Bruce
author_sort Nelson, Delia
collection PubMed
description Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.
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spelling pubmed-40521712014-06-22 The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment Nelson, Delia Fisher, Scott Robinson, Bruce J Immunol Res Review Article Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients. Hindawi Publishing Corporation 2014 2014-05-18 /pmc/articles/PMC4052171/ /pubmed/24955376 http://dx.doi.org/10.1155/2014/789069 Text en Copyright © 2014 Delia Nelson et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Nelson, Delia
Fisher, Scott
Robinson, Bruce
The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title_full The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title_fullStr The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title_full_unstemmed The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title_short The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment
title_sort “trojan horse” approach to tumor immunotherapy: targeting the tumor microenvironment
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052171/
https://www.ncbi.nlm.nih.gov/pubmed/24955376
http://dx.doi.org/10.1155/2014/789069
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