Published in

Frontiers Media, Frontiers in Immunology, (14), 2023

DOI: 10.3389/fimmu.2023.1121030

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Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells

Journal article published in 2023 by Michael Hiltensperger ORCID, Angela M. Krackhardt
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Adoptive cell therapy (ACT) has seen a steep rise of new therapeutic approaches in its immune-oncology pipeline over the last years. This is in great part due to the recent approvals of chimeric antigen receptor (CAR)-T cell therapies and their remarkable efficacy in certain soluble tumors. A big focus of ACT lies on T cells and how to genetically modify them to target and kill tumor cells. Genetically modified T cells that are currently utilized are either equipped with an engineered CAR or a T cell receptor (TCR) for this purpose. Both strategies have their advantages and limitations. While CAR-T cell therapies are already used in the clinic, these therapies face challenges when it comes to the treatment of solid tumors. New designs of next-generation CAR-T cells might be able to overcome these hurdles. Moreover, CARs are restricted to surface antigens. Genetically engineered TCR-T cells targeting intracellular antigens might provide necessary qualities for the treatment of solid tumors. In this review, we will summarize the major advancements of the CAR-T and TCR-T cell technology. Moreover, we will cover ongoing clinical trials, discuss current challenges, and provide an assessment of future directions within the field.