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Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy

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Abstract

Fibroblast activation protein (FAP) is a serine protease with dual enzymatic activities overexpressed in cancer-associated fibroblasts (CAFs) in several tumor types, while its expression in healthy adult tissues is scarce. FAP overexpression on CAFs is associated with poor prognosis and plays an important role in tumor development, progression, and invasion. Therefore, FAP is considered a robust therapeutic target for cancer therapy. Here, we try to review and highlight the recent advances in immunotherapies for FAP targeting including the anti-FAP antibodies and immunoconjugates, FAP chimeric antigen receptor (CAR)-T cell, and various FAP vaccines in a preclinical and clinical setting. Subsequently, a discussion on the challenges and prospects associated with the development and translation of effective and safe therapies for targeting and depletion of FAP is provided. We proposed that new CAR-T cell engineering strategies and nanotechnology-based systems as well as advanced functional biomaterials can be used to improve the efficiency and safety of CAR-T cells and vaccines against FAP for more personalized immunotherapy. This review emphasizes the immune targeting of FAP as an emerging stromal candidate and one of the crucial elements in immunotherapy and shows the potential for improvement of current cancer therapy.

Graphical Abstract

A summary of different immunotherapy approaches to target fibroblast activation protein (FAP) for cancer therapy

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Acknowledgements

Graphical abstract, Fig. 1, and panels B and C in Fig. 2 were drawn with Biorender software. The authors would like to acknowledge the Nanotechnology Research Center, Mashhad University of Medical Sciences (MUMS).

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Authors and Affiliations

  1. Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

    Sedigheh Shahvali, Niloufar Rahiman, Mahmoud Reza Jaafari & Leila Arabi

  2. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Reza Jaafari & Leila Arabi

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  1. Sedigheh Shahvali
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Leila Arabi had the idea for the article; Sedigheh Shahvali, Niloufar Rahiman, and Leila Arabi performed the literature search and data analysis; and Leila Arabi and Mamhmoud Reza Jaafari critically revised the work.

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Correspondence to Leila Arabi.

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Shahvali, S., Rahiman, N., Jaafari, M.R. et al. Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy. Drug Deliv. and Transl. Res. 13, 2041–2056 (2023). https://doi.org/10.1007/s13346-023-01308-9

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