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Review
. 2022 Nov 24;10(12):3035.
doi: 10.3390/biomedicines10123035.

Cutting-Edge CAR Engineering: Beyond T Cells

Luisa Chocarro  1 , Ester Blanco  1   2 , Leticia Fernández-Rubio  1 , Hugo Arasanz  1   3 , Ana Bocanegra  1 , Miriam Echaide  1 , Maider Garnica  1 , Pablo Ramos  1 , Sergio Piñeiro-Hermida  1 , Ruth Vera  3 , Grazyna Kochan  1 , David Escors  1
Affiliations
Review

Cutting-Edge CAR Engineering: Beyond T Cells

Luisa Chocarro et al. Biomedicines. .

Abstract

Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the immunosuppressive tumour microenvironment (TME). In the TME, cells of the myeloid lineage (M) are among the immunosuppressive cell types with the highest tumour infiltration rate. These cells interact with other immune cells, mediating immunosuppression and promoting angiogenesis. Recently, the development of CAR-M cell therapies has been put forward as a new candidate immunotherapy with good efficacy potential. This alternative CAR strategy may increase the efficacy, survival, persistence, and safety of CAR treatments in solid tumours. This remains a critical frontier in cancer research and opens up a new possibility for next-generation personalised medicine to overcome TME resistance. However, the exact mechanisms of action of CAR-M and their effect on the TME remain poorly understood. Here, we summarise the basic, translational, and clinical results of CAR-innate immune cells and CAR-M cell immunotherapies, from their engineering and mechanistic studies to preclinical and clinical development.

Keywords: CAR-NK; CAR-macrophage; CAR-monocyte; CAR-myeloid; immunotherapy; tumour microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CAR structure.
Figure 2
Figure 2
Emerging strategies in targeting TAMCs. Schematic representation of main strategies described above.
Figure 3
Figure 3
Detailed analysis of the CAR-NK clinical landscape. Pie charts with categorisation of CAR-NK clinical trials by status and study design as indicated (phase, masking, allocation, intervention model assignment, status and age). All current CAR-NK trials are interventional.
Figure 4
Figure 4
Detailed analysis of the CAR-M clinical landscape. Pie charts with categorisation of CAR-NK clinical trials by status and study design as indicated (phase, masking, allocation, intervention model assignment, status, age and study type).
See this image and copyright information in PMC

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