Völzke Christina, Ehrhardt Lisa, Fischer Laura, Maul Peter, Wenzel Carina, Riabinska Arina, Criado-Moronati Elvira, Dienstbier Mike, Hassel Jessica, Zhang Danmei, Haanen John B, Handgretinger Rupert, Hardy Ian R, Heemskerk Bianca, Dzionek Andrzej
Research and Development, Miltenyi Biotec, Bergisch Gladbach, Germany.
Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
Front Immunol. 2024 Dec 9;15:1483254. doi: 10.3389/fimmu.2024.1483254. eCollection 2024.
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 1x10 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.
最近的研究揭示了肿瘤浸润淋巴细胞（TILs）有效且安全地治疗实体瘤的潜力。然而，TIL疗法在患者中的应用仍受到非标准化且繁琐的制造程序的阻碍，这些程序成本高昂且会产生高度可变的细胞产品。为了解决这些限制，已经开发了CliniMACS Prodigy肿瘤反应性T细胞（TRT）工艺。TRT工艺允许在符合GMP条件的临床合规且封闭的系统中自动分离、转导和扩增肿瘤反应性T细胞。TRT工艺可以使用多种反映临床相关应用的方法来生成肿瘤反应性T细胞。它可以使用符合GMP标准的试剂管理自动化快速扩增方案（REP），以从包括黑色素瘤在内的实体瘤中生成TIL细胞产品。此外，TRT工艺可直接从肿瘤消化物中自动封闭选择表达CD137的TILs，然后直接扩增所选细胞。即使在REP阶段接种的TILs少至1×10时，富集的CD137 TILs也能得到强劲扩增。这些数据为在CliniMACS Prodigy中以封闭、自动化的方式从肿瘤消化物中分离和扩增肿瘤反应性T细胞提供了概念验证，从而实现了TIL产品的高效、简单且可重复的制造。从肿瘤消化物中直接选择CD137 TILs无需预REP阶段，选择了具有治疗相关性的细胞，并且与传统方法相比可以显著缩短制造时间。
