Locoregional delivery of CAR-T cells in the clinic

Locoregional delivery of CAR-T cells in the clinic.

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Item Type: Review
Status: Published
Official URL: https://doi.org/10.1016/j.phrs.2022.106329
Journal or Publication Title: Pharmacological Research
Volume: 182
Page Range: p. 106329
Date: 27 June 2022
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1016/j.phrs.2022.106329
ISSN: 10436618
Date Deposited: 26 Sep 2022 00:16

Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological malignancies. Unfortunately, this success has not been replicated in solid tumors, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Many preclinical studies have focused on improvements to CAR design to try to overcome some of these hurdles. However, a growing body of work has also focused on the use of local and/or regional delivery of CAR-T cells as a means to overcome poor T cell trafficking and inefficient T cell penetration into tumors. Most trials that incorporate locoregional delivery of CAR-T cells have targeted tumors of the central nervous system - repurposing an Ommaya/Rickham reservoir for repeated delivery of cells directly to the tumor cavity or ventricles. Hepatic artery infusion is another technique used for locoregional delivery to hepatic tumors. Locoregional delivery theoretically permits increased numbers of CAR-T cells within the tumor while reducing the risk of immune-related systemic toxicity. Studies to date have been almost exclusively phase I. The growing body of evidence indicates that locoregional delivery of CAR-T cells is both safe and feasible. This review focuses specifically on the use of locoregional delivery of CAR-T cells in clinical trials.

Sagnella, Sharon M.
White, Amy L.
Yeo, Dannel
Saxena, Payal
van Zandwijk, Nico
Rasko, John E.J.
Last Modified: 26 Sep 2022 00:16
URI: https://eprints.centenary.org.au/id/eprint/1263

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