Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines

The development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine...

Full description

Saved in:
Bibliographic Details
Main Authors: Renee N Donahue, Jeffrey Schlom, James L Gulley, James W Hodge, Claudia Palena, Duane H Hamilton, Sofia R Gameiro
Format: Article
Language:English
Published: BMJ Publishing Group 2024-07-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/7/e009595.full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850235195166294016
author Renee N Donahue
Jeffrey Schlom
James L Gulley
James W Hodge
Claudia Palena
Duane H Hamilton
Sofia R Gameiro
author_facet Renee N Donahue
Jeffrey Schlom
James L Gulley
James W Hodge
Claudia Palena
Duane H Hamilton
Sofia R Gameiro
author_sort Renee N Donahue
collection DOAJ
description The development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine development and delivery also has some drawbacks, including the level of effort to develop a patient-specific product, accuracy of algorithms to predict neoepitopes, and with the exception of melanoma and some other tumor types, biopsies of metastatic lesions of solid tumors are often not available. We hypothesize that in some circumstances the use of rationally designed combinations of “off-the-shelf” agents may prove an additional path to enable the patient to produce his/her own “neoepitope vaccine” in situ. These combination therapies may consist of agents to activate a tumor-associated T-cell response, potentiate that response, reduce or eliminate immunosuppressive entities in the tumor microenvironment, and/or alter the phenotype of tumor cells to render them more susceptible to immune-mediated lysis. Examples are provided in both preclinical and clinical studies in which combinations of “off-the-shelf” agents lead to the generation of T cells directed against tumor-derived neoepitopes with consequent antitumor activity.
format Article
id doaj-art-a0dfb2ad06104e178521dabe0f22daa7
institution OA Journals
issn 2051-1426
language English
publishDate 2024-07-01
publisher BMJ Publishing Group
record_format Article
series Journal for ImmunoTherapy of Cancer
spelling doaj-art-a0dfb2ad06104e178521dabe0f22daa72025-08-20T02:02:20ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2024-009595Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccinesRenee N Donahue0Jeffrey Schlom1James L Gulley2James W Hodge3Claudia Palena4Duane H Hamilton5Sofia R Gameiro61Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA2Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA1National Cancer Institute, Bethesda, MD, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USAThe development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine development and delivery also has some drawbacks, including the level of effort to develop a patient-specific product, accuracy of algorithms to predict neoepitopes, and with the exception of melanoma and some other tumor types, biopsies of metastatic lesions of solid tumors are often not available. We hypothesize that in some circumstances the use of rationally designed combinations of “off-the-shelf” agents may prove an additional path to enable the patient to produce his/her own “neoepitope vaccine” in situ. These combination therapies may consist of agents to activate a tumor-associated T-cell response, potentiate that response, reduce or eliminate immunosuppressive entities in the tumor microenvironment, and/or alter the phenotype of tumor cells to render them more susceptible to immune-mediated lysis. Examples are provided in both preclinical and clinical studies in which combinations of “off-the-shelf” agents lead to the generation of T cells directed against tumor-derived neoepitopes with consequent antitumor activity.https://jitc.bmj.com/content/12/7/e009595.full
spellingShingle Renee N Donahue
Jeffrey Schlom
James L Gulley
James W Hodge
Claudia Palena
Duane H Hamilton
Sofia R Gameiro
Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
Journal for ImmunoTherapy of Cancer
title Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
title_full Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
title_fullStr Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
title_full_unstemmed Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
title_short Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines
title_sort hypothesis the generation of t cells directed against neoepitopes employing immune mediating agents other than neoepitope vaccines
url https://jitc.bmj.com/content/12/7/e009595.full
work_keys_str_mv AT reneendonahue hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT jeffreyschlom hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT jameslgulley hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT jameswhodge hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT claudiapalena hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT duanehhamilton hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines
AT sofiargameiro hypothesisthegenerationoftcellsdirectedagainstneoepitopesemployingimmunemediatingagentsotherthanneoepitopevaccines