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Review
. 2021 Aug 5:10:313-323.
doi: 10.2147/ITT.S291767. eCollection 2021.

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

Reyisa Bughda  1 , Paraskevi Dimou  1 , Reena R D'Souza  1 , Astero Klampatsa  1
Affiliations
Review

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

Reyisa Bughda et al. Immunotargets Ther. .

Abstract

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; fibroblast-activating-protein; fibroblasts; immunotherapy; solid tumors; stroma; tumor microenvironment.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
FAP expression in cancer tissue. Strong FAP expression (red) is observed in the stromal cells (CAFs) of a human squamous cell carcinoma stained with anti-FAP rabbit polyclonal antibody (dilution 1:100) IHC (20X image).
Figure 2
Figure 2
Anti-FAP CAR-T cells in the solid tumor TME. (A) The anti-FAP CAR constructs consist of an anti-FAP targeting moiety (scFv), a spacer, a transmembrane domain (TM), and signaling domains (CD28/41BB and CD3ζ). These are transduced and expressed on T cells. The developed anti-FAP CAR-T cells can then bind to FAP expressed on CAFs. (B) Binding of anti-FAP CAR-T cells to FAP on CAFs within the hostile, multicellular TME.
See this image and copyright information in PMC

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