IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors.
Biomarkers, Tumor
Combined Modality Therapy
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Immune Checkpoint Proteins
/ metabolism
Immunotherapy, Adoptive
/ methods
Interleukin-15
/ administration & dosage
Lymphocytes, Tumor-Infiltrating
/ drug effects
Neoplasms
/ etiology
Treatment Outcome
CAR T cells
IL-15
T(CM)
TCF1
TCF7
anti-PD-1
cancer
checkpoint blockade
solid tumor
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
04 11 2020
04 11 2020
Historique:
received:
28
04
2020
revised:
24
06
2020
accepted:
10
07
2020
pubmed:
1
8
2020
medline:
12
8
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8
Identifiants
pubmed: 32735774
pii: S1525-0016(20)30369-5
doi: 10.1016/j.ymthe.2020.07.018
pmc: PMC7647667
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
Immune Checkpoint Proteins
0
Interleukin-15
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2379-2393Informations de copyright
Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
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