Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma

Fibroblast activation protein (FAP) is a membrane protease that is highly expressed by cancer-associated fibroblasts (CAFs). FAP can modulate the tumor microenvironment (TME) by remodeling the extracellular matrix (ECM), and its overexpression on CAFs is associated with poor prognosis in various can...

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Bibliographic Details
Published in:ImmunoTargets and therapy 2021-01, Vol.10, p.313-323
Main Authors: Bughda, Reyisa, Dimou, Paraskevi, D'Souza, Reena R, Klampatsa, Astero
Format: Article
Language:English
Subjects:
Antigens
B cells
Biomarkers
Cancer
car t-cells
Care and treatment
Cell therapy
Chimeric antigen receptors
Clinical trials
Cytokines
Cytotoxicity
Epidermal growth factor
Extracellular matrix
Fibroblast activation protein
fibroblast-activating-protein
Fibroblasts
Hematology
Immunotherapy
Leukemia
Lymphocytes
Lymphocytes T
Lymphoma
Medical research
Medicine, Experimental
Membrane proteins
Patients
Prognosis
Prostate
Proteases
Response rates
Review
Solid tumors
Stroma
T cell receptors
T cells
Tumor microenvironment
Tumors
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Summary:Fibroblast activation protein (FAP) is a membrane protease that is highly expressed by cancer-associated fibroblasts (CAFs). FAP can modulate the tumor microenvironment (TME) by remodeling the extracellular matrix (ECM), and its overexpression on CAFs is associated with poor prognosis in various cancers. The TME is in part accountable for the limited efficacy of chimeric antigen receptor (CAR)-T cell therapy in treatment of solid tumors. Targeting FAP with CAR-T cells is one of the strategies being researched to overcome the challenges in the TME. This review describes the role of FAP in the TME and its potential as a target in CAR-T cell immunotherapy, summarizes the preclinical studies and clinical trials of anti-FAP-CAR-T cells to date, and reviews possible optimizations to augment their cytotoxic efficiency in solid tumors. Keywords: CAR T-cells, immunotherapy, tumor microenvironment, fibroblasts, fibroblast-activating-protein, solid tumors, stroma
ISSN:2253-1556
2253-1556
DOI:10.2147/ITT.S291767