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Abstract 2329: Clinical manufacturing of CAR T cells targeting ICAM-1 for a phase I study against advanced thyroid cancer therapy

Background: Patients with anaplastic or poorly differentiated recurrent thyroid carcinomas have a poor prognosis, with a median survival of Methods: We have chosen to use CliniMACS Prodigy system for a closed, automated, and robust CAR T cell manufacturing process. Using a cryopreserved leukopak, TCT v2.0 protocol began with rapidly thawing the leukopak while directly welded to the Prodigy. T cell lentivirus transduction was performed 2x, 24 and 48 hr post activation. CAR T cells were released after ~10 days of culture and cryopreserved in ready-to-infuse formulation (AIC100). Products were then subject to in vitro cytotoxicity, in vivo efficacy and safety in xenografted mice with ATC cells (8505C), and PET/CT imaging using 18F-NOTA-octreotide to detect T cell dynamics. Results: Prodigy manufactured CAR T cells were subjected to qualification and functional assays (n=7): cell viability, cell number, CAR expression, virus copy number (VCN), T cell subset and phenotype, and E to T assays. Consistent with reported values for Prodigy, our manufacturing protocol produced 55±9% transduction rate, 96±1.8% viability, and 2.9±0.7x10^9 final cell number. The VCN was in the range of 1.0-2.1, below the criteria of 100 days). Conclusions: Selective anti-tumor activity in the absence of toxicity provides proof-of-concept that micromolar affinity tuned CAR T cells can be used to target tumors expressing high levels of antigen while avoiding normal tissues expressing basal levels of the same antigen. These studies support the initiation of a phase I study to examine the safety and potential efficacy of micromolar affinity tuned CAR T cells against newly diagnosed anaplastic and refractory or recurrent thyroid cancers. Citation Format: Yogindra Vedvyas, Jaclyn E. McCloskey, Yanping Yang, Irene M. Min, Thomas J. Fahey, Yen-Michael S. Hsu, Jing-Mei Hsu, Koen V. Besien, Ian Gaudet, Ping Law, Joon Kim, Eric V. Hofe, Moonsoo M. Jin. Clinical manufacturing of CAR T cells targeting ICAM-1 for a phase I study against advanced thyroid cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2329.