Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?

Version 1 : Received: 30 November 2023 / Approved: 30 November 2023 / Online: 1 December 2023 (03:05:54 CET)

A peer-reviewed article of this Preprint also exists.

Lonez, C.; Breman, E. Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met? Cells 2024, 13, 146. Lonez, C.; Breman, E. Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met? Cells 2024, 13, 146.

Abstract

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this therapy to other malignancies and broader patient populations. However, several limitations remain, including those associated with the time-consuming and highly personalized manufacturing of autologous CAR-Ts. Technologies to establish “off-the-shelf” allogeneic CAR-Ts with low alloreactivity are currently being developed, with a strong focus on gene editing technologies. Although these technologies have many advantages, they have also strong limitations including double-strand breaks in the DNA with associated multiple safety risks as well as the lack of modulation. As an alternative, non-gene editing technologies provide an interesting approach to support the development of allogeneic CAR-Ts in the future, with possibilities of fine-tuning gene expression and easy development. Here we will review the different ways allogeneic CAR-Ts can be manufactured and discuss which technologies are currently used. The biggest hurdles for successful therapy of allogeneic CAR-Ts will be summarized and finally an overview of the current clinical evidence for allogeneic CAR-Ts in comparison to its autologous counterpart will be given.

Keywords

allogeneic; chimeric antigen receptor; off-the-shelf; gene editing

Subject

Medicine and Pharmacology, Immunology and Allergy

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