Clinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system
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 va...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483254/full |
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| Summary: | 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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| ISSN: | 1664-3224 |