An effective mouse model for adoptive cancer immunotherapy targeting neoantigens.
JCI Insight
; 4(10)2019 05 16.
Article
em En
| MEDLINE
| ID: mdl-31092734
ABSTRACT
The adoptive cell transfer (ACT) of T cells targeting mutated neoantigens can cause objective responses in varieties of metastatic cancers, but the development of new T cell-based treatments relies on accurate animal models. To investigate the therapeutic effect of targeting a neoantigen with ACT, we used T cells from pmel-1 T cell receptor-transgenic mice, known to recognize a WT peptide, gp100, and a mutated version of the peptide that has higher avidity. We gene-engineered B16 cells to express the WT or mutated gp100 epitopes and found that pmel-1-specific T cells targeting a neoantigen tumor target augmented recognition as measured by IFN-γ production. Neoantigen expression by B16 also enhanced the capacity of pmel-1 T cells to trigger the complete and durable regression of large, established, vascularized tumor and required less lymphodepleting conditioning. Targeting neoantigen uncovered the possibility of using enforced expression of the IL-2Rα chain (CD25) in mutation-reactive CD8+ T cells to improve their antitumor functionality. These data reveal that targeting of "mutated-self" neoantigens may lead to improved efficacy and reduced toxicities of T cell-based cellular immunotherapies for patients with cancer.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
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Fatores Imunológicos
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Antígenos de Neoplasias
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article