4.8 Review

Impact of Manufacturing Procedures on CAR T Cell Functionality

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.876339

Keywords

CAR T cell; ex vivo expansion; culture media; serum; cytokines; pharmacological inhibitor; manufacturing time; cryopreservation

Categories

Funding

  1. National Heart, Lung, and Blood Institute [5T32HL092332-17]
  2. National Cancer Institute [F99CA253757]
  3. Cancer Prevention and Research Institute of Texas [HIHR RP210158]

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CAR T cell therapy has shown promising success in cancer treatment, with ex vivo culture conditions being a crucial factor in impacting CAR T cell functionality.
The field of chimeric antigen receptor (CAR) modified T cell therapy has rapidly expanded in the past few decades. As of today, there are six CAR T cell products that have been approved by the FDA: KYMRIAH (tisagenlecleucel, CD19 CAR T cells), YESCARTA (axicabtagene ciloleucel, CD19 CAR T cells), TECARTUS (brexucabtagene autoleucel, CD19 CAR T cells), BREYANZI (lisocabtagene maraleucel, CD19 CAR T cells), ABECMA (idecabtagene vicleucel, BCMA CAR T cells) and CARVYKTI (ciltacabtagene autoleucel, BCMA CAR T cells). With this clinical success, CAR T cell therapy has become one of the most promising treatment options to combat cancers. Current research efforts focus on further potentiating its efficacy in non-responding patients and solid tumor settings. To achieve this, recent evidence suggested that, apart from developing next-generation CAR T cells with additional genetic modifications, ex vivo culture conditions could significantly impact CAR T cell functionality - an often overlooked aspect during clinical translation. In this review, we focus on the ex vivo manufacturing process for CAR T cells and discuss how it impacts CAR T cell function.

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