Establishing a GMP-compliant manufacturing process and phase-appropriate analytics for early development of a FiCAR T-cell product with a novel CAR spacer

Establishing a GMP-compliant manufacturing process and phase-appropriate analytics for early development of a FiCAR T-cell product with a novel CAR spacer

Abstract There is a growing demand for chimeric antigen receptor (CAR) -T cells for clinical trials. Consequently, new centers capable of manufacturing advanced therapy medicinal products (ATMPs) are needed. In this study, we established a good manufacturing practice -compliant manufacturing process...

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Main Authors: Annu Luostarinen, Arja Vuorela, Erja Kerkelä, Mimmi Patrikoski, Annika Kotovuori, Jan Koski, Jonna Ahoniemi, Kaarina Lähteenmäki, Jenni Lehtisalo, Terhi Oja, Henrik Paavilainen, Anu Autio, Marie Nyman, Veera Nikoskelainen, Virginie Kergourlay, Endrit Elbasani, Bert van Veen, Anil Thotakura, Hector Monzo, Päivi M. Ojala, Matti Korhonen, Heidi Hongisto, Anita Laitinen
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
Subjects:
CAR T-cell
ATMP
Early development
Manufacturing
Analytical testing
Online Access:https://doi.org/10.1038/s41598-025-92736-9
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Summary:Abstract There is a growing demand for chimeric antigen receptor (CAR) -T cells for clinical trials. Consequently, new centers capable of manufacturing advanced therapy medicinal products (ATMPs) are needed. In this study, we established a good manufacturing practice -compliant manufacturing process and phase-appropriate analytics for a novel autologous CD19-targeted CAR T-cell product, 19-FiCART. We evaluated the stability of fresh, healthy donor-derived leukapheresis products (LPs), produced 19-FiCART using a 12-day semi-automated process with CD4/CD8-positive cell enrichment and lentiviral transduction, and evaluated the in vivo efficacy of 19-FiCART in a xenograft mouse lymphoma model. The optimal hold time and temperature to maintain LP stability were up to 73 h at 2–8 °C. The 19-FiCART manufacturing process consistently yielded more than 2 × 109 highly viable CAR+ T cells, which is considered sufficient for a clinical product. The 19-FiCART products also demonstrated potent anti-tumor activity both in vitro and in vivo. This paper provides a detailed description of the manufacturing process and analytics for 19-FiCART and provides insights into the development of a release strategy for novel CAR T-cell products intended for early clinical studies. Additionally, we present data on LP stability, which has broader implications for the development of various immune cell-based ATMPs.
ISSN:2045-2322

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