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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1483254
This article is part of the Research Topic Community Series in Personalized Immunotherapy: Advancing Processes to Extend Patient Collectives, Volume II View all 5 articles

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

Provisionally accepted
Christina Völzke Christina Völzke 1Lisa Ehrhardt Lisa Ehrhardt 1Laura Fischer Laura Fischer 2Peter Maul Peter Maul 1Carina Wenzel Carina Wenzel 1Arina Riabinska Arina Riabinska 1Elvira Criado-Moronati Elvira Criado-Moronati 1Mike Dienstbier Mike Dienstbier 1Danmei Zhang Danmei Zhang 3Jessica Hassel Jessica Hassel 4John B.A.G. Haanen John B.A.G. Haanen 5Rupert Handgtretinger Rupert Handgtretinger 6Ian Hardy Ian Hardy 1Bianca Heemskerk Bianca Heemskerk 7Andrzej Dzionek Andrzej Dzionek 1*
  • 1 Miltenyi Biotec, Bergisch Gladbach, Germany
  • 2 Immatics Biotechnologies (Germany), Tübingen, Baden-Württemberg, Germany
  • 3 LMU Munich University Hospital, Munich, Bavaria, Germany
  • 4 National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Baden-Württemberg, Germany
  • 5 The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands
  • 6 University Children's Hospital Tübingen, Tuebingen, Germany
  • 7 BioNTech (Germany), Mainz, Rhineland-Palatinate, Germany

The final, formatted version of the article will be published soon.

    Recent studies have revealed the potential of tumour-infiltrating lymphocytes (TILs) to treat solid tumours 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 tumour-reactive T cells in a clinically compliant and closed system under GMP conditions.The TRT Process can generate tumour-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 tumours, including melanoma. Additionally, the TRT Process automates the closed selection of CD137-expressing TILs directly from tumour digest followed by the direct expansion of selected cells. Enriched CD137 + TILs could be robustly expanded even when as few as 1x10 4 TILs were used to seed the REP phase. These data provide proof-of-concept for the isolation and expansion of tumour-reactive T cells from tumour 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 tumour 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.

    Keywords: tumour reactive T cells, CD137, TILs, CliniMACS Prodigy, REP, GMP compliant cell manufacturing, Automation

    Received: 19 Aug 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Völzke, Ehrhardt, Fischer, Maul, Wenzel, Riabinska, Criado-Moronati, Dienstbier, Zhang, Hassel, Haanen, Handgtretinger, Hardy, Heemskerk and Dzionek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Andrzej Dzionek, Miltenyi Biotec, Bergisch Gladbach, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.