Faculty, Staff and Student Publications

Publication Date

7-24-2025

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms26157151

PMID

40806287

PMCID

PMC12346291

PubMedCentral® Posted Date

7-24-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 109 viable TIL cells, with a median yield of 1.1 × 1010 cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC.

Published Open-Access

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