Cutting-edge CAR engineering: beyond T cells

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 with...

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Detalles Bibliográficos
Autores: Chocarro de Erauso, Luisa, Blanco, Ester, Fernández Rubio, Leticia, Arasanz Esteban, Hugo, Bocanegra Gondán, Ana Isabel, Echaide Górriz, Míriam, Garnica, Maider, Ramos, Pablo, Piñeiro Hermida, Sergio, Vera García, Ruth, Kochan, Grazyna, Escors Murugarren, David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/45147
Acceso en línea:https://hdl.handle.net/2454/45147
Access Level:acceso abierto
Palabra clave:CAR-macrophage
CAR-monocyte
CAR-myeloid
CAR-NK
Immunotherapy
Tumour microenvironment
Descripción
Sumario: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.