Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system

Autor: Christina Völzke, Lisa Ehrhardt, Laura Fischer, Peter Maul, Carina Wenzel, Arina Riabinska, Elvira Criado-Moronati, Mike Dienstbier, Jessica Hassel, Danmei Zhang, John B. Haanen, Rupert Handgretinger, Ian R. Hardy, Bianca Heemskerk, Andrzej Dzionek
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Immunology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2024.1483254
Popis: Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy® Tumor Reactive T cell (TRT) Process has been developed. The TRT Process allows the automated isolation, transduction, and expansion of tumor-reactive T cells in a clinically compliant and closed system under GMP conditions. The TRT Process can generate tumor-reactive T cells using several methodologies which reflect clinically relevant applications. It can manage an automated Rapid Expansion Protocol (REP) using GMP-compliant reagents to generate a TIL cell product from solid tumors, including melanoma. Additionally, the TRT Process automates the closed selection of CD137-expressing TILs directly from tumor digest followed by the direct expansion of selected cells. Enriched CD137+ TILs could be robustly expanded even when as few as 1x104 TILs were used to seed the REP phase. These data provide proof-of-concept for the isolation and expansion of tumor-reactive T cells from tumor digest in a closed, automated manner in the CliniMACS Prodigy, allowing for an efficient, simple, and reproducible manufacturing of TIL products. The direct selection of CD137+ TILs from tumor digest removes the need for the pre-REP phase, selects for therapeutically relevant cells, and can dramatically shorten the manufacturing time compared to conventional methods.
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