Generation and Characterization of Ex Vivo Expanded Tumor-infiltrating Lymphocytes From Renal Cell Carcinoma Tumors for Adoptive Cell Therapy.
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
07
03
2024
accepted:
03
06
2024
medline:
12
7
2024
pubmed:
12
7
2024
entrez:
12
7
2024
Statut:
aheadofprint
Résumé
Autologous therapeutic tumor-infiltrating lymphocyte (TIL) therapy is a promising strategy to enhance antitumor immunity. Optimization of ex vivo TIL expansion could expand current immunotherapy options. Previous attempts to generate TIL in renal cell carcinoma (RCC) have been technically challenging. We applied a second-generation manufacturing process, currently used to generate the melanoma TIL product lifileucel, in RCC. Resected primary and metastatic RCC samples were processed using the Gen 2 manufacturing process comprising of pre-Rapid Expansion Protocol (pre-REP) and REP steps. We assessed REP TILs for viability and performed phenotypic and functional characterization. We correlated the tumor immune microenvironment (TIME) with successful TIL expansion. Eight of 11 RCC samples underwent successful REP. Three failed cases demonstrated low CD8/FoxP3 ratio and high expression of PD-1 within FoxP3 cells. Expression of exhaustion markers differed between the TIME and expanded TILs; the latter had a TIM3-high/PD-1-low phenotype but retained functional capacity comparable to lifileucel. The Gen 2 manufacturing process used for lifileucel successfully expanded functional TILs from RCC samples, enabling further study in a clinical trial. TIME features such as low CD8/FoxP3 ratio and high PD-1 expression within FoxP3 cells warrant study as potential biomarkers of successful TIL expansion.
Identifiants
pubmed: 38995718
doi: 10.1097/CJI.0000000000000533
pii: 00002371-990000000-00115
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
D.J.E., S.S., and D.F.M. are supported by P50 CA101942 SPORE in Kidney Cancer (PIs: D.F.M. and Kaelin). D.J.E. reports research funding to institution from Bristol-Myers Squibb, Cardiff Oncology, MiNK Therapeutics, Novartis, Puma Biotechnology, and Sanofi; consulting honorarium from Nimbus Therapeutics; discounted research sequencing from Foundation Medicine. C.H., K.O., A.W., B.B., and A.N. are employed by and hold stock in Iovance. AV was employed by and held stock in Iovance at the time of data acquisition. S.S. reports receiving commercial research grants from Bristol-Myers Squibb, AstraZeneca, Exelixis and Novartis; is a consultant/advisory board member for Merck, AstraZeneca, Bristol Myers Squibb, CRISPR Therapeutics AG, AACR, and NCI; receives royalties from Biogenex; and mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components. D.F.M. reports research support from Alkermes, Bristol-Myers Squibb, Exelixis, Genentech, Merck, Pfizer, and X4 Pharma; consulting honoraria from Aveo, Bristol-Myers Squibb, Cullinan, Eisai, Exelixis, Genentech, Merck, Pfizer, and Xilio. All other authors have declared that there are no financial conflicts of interest with regard to this work.
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