Tumour burden and antigen-specific T cell magnitude represent major parameters for clinical response to cancer vaccine and TCR-engineered T cell therapy.
Adoptive T cell therapy
Cancer vaccines
Immunotherapy
T cells
Tumour burden
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
25
01
2022
revised:
18
03
2022
accepted:
17
05
2022
pubmed:
18
6
2022
medline:
20
7
2022
entrez:
17
6
2022
Statut:
ppublish
Résumé
Cancer vaccines and T-cell receptor (TCR) engineered T cells (Tg-T cell) represent two different therapeutic strategies that can target the same tumour epitopes. The first approach requires the induction of a specific immune response in patients, while the second relies on the efficacy of adoptively transferred T cells. Because the ratio of antigen-specific T cells to tumour cells engaged by these strategies may influence the clinical outcome, we evaluated the efficacy of these two therapeutic approaches in solid tumours according to the tumour burden. We performed a meta-analysis restricted to the therapeutic vaccine and Tg-T cell trials, presenting annotated individual clinical data. We adapted a previously published mathematical model for tumour immune dynamics to estimate the clinical impact of the number of specific T cells in regard to the tumour burden. A focused analysis of Tg-T cell studies revealed that clinical responses were mostly observed with the highest doses of infused T cells, suggesting that exceeding a threshold of effector T cells may be required for clinical efficacy. In silico modelling of cancer vaccine and Tg-T cell therapies starting at different tumour burdens showed that therapeutic vaccines control low or moderate tumour burdens, whereas increasing the amount of infused Tg-T cells succeeds in controlling high tumour masses. We propose that therapeutic vaccines should be considered in the context of low or moderate tumour burden, whereas Tg-T cell strategies may be more adapted for the treatment of advanced metastatic diseases.
Sections du résumé
BACKGROUND
Cancer vaccines and T-cell receptor (TCR) engineered T cells (Tg-T cell) represent two different therapeutic strategies that can target the same tumour epitopes. The first approach requires the induction of a specific immune response in patients, while the second relies on the efficacy of adoptively transferred T cells. Because the ratio of antigen-specific T cells to tumour cells engaged by these strategies may influence the clinical outcome, we evaluated the efficacy of these two therapeutic approaches in solid tumours according to the tumour burden.
METHODS
We performed a meta-analysis restricted to the therapeutic vaccine and Tg-T cell trials, presenting annotated individual clinical data. We adapted a previously published mathematical model for tumour immune dynamics to estimate the clinical impact of the number of specific T cells in regard to the tumour burden.
RESULTS
A focused analysis of Tg-T cell studies revealed that clinical responses were mostly observed with the highest doses of infused T cells, suggesting that exceeding a threshold of effector T cells may be required for clinical efficacy. In silico modelling of cancer vaccine and Tg-T cell therapies starting at different tumour burdens showed that therapeutic vaccines control low or moderate tumour burdens, whereas increasing the amount of infused Tg-T cells succeeds in controlling high tumour masses.
CONCLUSION
We propose that therapeutic vaccines should be considered in the context of low or moderate tumour burden, whereas Tg-T cell strategies may be more adapted for the treatment of advanced metastatic diseases.
Identifiants
pubmed: 35714452
pii: S0959-8049(22)00286-6
doi: 10.1016/j.ejca.2022.05.008
pii:
doi:
Substances chimiques
Cancer Vaccines
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
96-105Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.