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Review
. 2022 Jul 12;17(3):134.
doi: 10.3892/mco.2022.2567. eCollection 2022 Sep.

Advances and challenges of CAR T therapy and suitability of animal models (Review)

Xavier E Ramos-Cardona  1 , Weichuan Luo  2 , Sulma I Mohammed  1
Affiliations
Review

Advances and challenges of CAR T therapy and suitability of animal models (Review)

Xavier E Ramos-Cardona et al. Mol Clin Oncol. .

Abstract

Chimeric antigen receptors (CARs) recently gained momentum in cancer treatment due to their ability to promote T-cell mediated responses to a specific tumor-associated antigen. CARs are part of the adoptive cell transfer (ACT) strategies that utilize patients' T lymphocytes, genetically engineered to kill cancer cells. However, despite the therapy's success against blood-related malignancies, treating solid tumors has not reached its fullest potential yet. The reasons include the complex suppressive tumor microenvironment, mutations on cancer cells' target receptors, lethal side-effects, restricted trafficking into the tumor, suboptimal persistence in vivo and the lack of animal models that faithfully resemble human tumor's immunological responses. Currently, rodent models are used to investigate the safety and efficacy of CAR therapies. However, these models are limited in representing the human disease faithfully, fail to predict the adverse treatment events and overestimate the efficacy of the therapy. On the other hand, spontaneously developed tumors in dogs are more suited in CAR research and their efficacy has been demonstrated in a number of diseases, including lymphoma, osteosarcoma and mammary tumors. The present review discusses the design and evolution of CARs, challenges of CAR in solid tumors, human and canine clinical trials and advantages of the canine model.

Keywords: canine; chimeric antigen receptors therapy; dog; hematological malignancies; immunotherapy; solid tumor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Schematic diagram of the advances and challenges of CAR-T cell therapy in animal models. General design of the chimeric receptor, trials and differences between hematological malignancies and solid tumors are discussed in the present review paper. In addition, comparison between different animals used as pre-clinical models are discussed presenting their potential translational impact in CAR-T cell development. CAR, chimeric antigen receptors.
See this image and copyright information in PMC

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