Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Construction and Functional Characterization of a Fully Human Anti-mesothelin Chimeric Antigen Receptor (CAR) Expressing T Cell

Sun Sep 25 08:34:16 2022

(2020) Construction and Functional Characterization of a Fully Human Anti-mesothelin Chimeric Antigen Receptor (CAR) Expressing T Cell. Iranian Journal of Allergy Asthma and Immunology. pp. 264-275. ISSN 1735-1502

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Abstract

Chimeric antigen receptor (CAR) T cell therapy is considered as an encouraging approach for the treatment of hematological malignancies. However, its efficacy in solid tumors has not been satisfying, mainly in the immunosuppressive network of the tumor microenvironment and paucity of appropriate target antigens. Mesothelin (MSLN) is a tumor-associated antigen (TAA) expressed in numerous types of solid tumors such as gastrointestinal, ovarian, and pancreatic tumors. Owing to high expression in tumor cells and low expression in normal tissues, MSLN-targeted therapies like monoclonal antibodies have been previously developed. In the present study, a CAR T cell harboring the second-generation of a fully human anti-MSLN-CAR construct containing CD3 zeta and 4-1BB signaling domains was produced and it was functionally evaluated against an MSLN-expressing cell line. The findings showed potent, specific proliferation, cytotoxic activity, and interleukin (IL)-2, Tumor necrosis factor-(TNF) alpha, and Interferon-(IFN) gamma production in an antigen-dependent manner. Cytotoxic activity was shown in effector-to-target ratio from 1:1 to 20:1, but the most adequate efficacy was observed in the ratio of 10:1. Non-specific activity against MSLN negative cell line was not observed. Our data demonstrated that primary human T cells expressing fully human MSLN-CAR construct are effective against MSLN-expressing cell lines in vitro, suggesting this MSLN-CAR construct as a potential therapeutic tool in a clinical setting.

Item Type: Article
Creators:
CreatorsEmail
Jafarzadeh, L.UNSPECIFIED
Masoumi, E.UNSPECIFIED
Alishah, K.UNSPECIFIED
Mirzaei, H. R.UNSPECIFIED
Jamali, A.UNSPECIFIED
Fallah-Mehrjardi, K.UNSPECIFIED
Rostamian, H.UNSPECIFIED
Khakpoor-Koosheh, M.UNSPECIFIED
Meshkani, R.UNSPECIFIED
Noorbakhsh, F.UNSPECIFIED
Hadjati, J.UNSPECIFIED
Keywords: Adoptive immunotherapy Chimeric antigen receptor Mesothelin antitumor-activity cd28 costimulation phase-i proliferation immunotherapy efficacy vivo Allergy Immunology
Divisions:
Page Range: pp. 264-275
Journal or Publication Title: Iranian Journal of Allergy Asthma and Immunology
Journal Index: ISI
Volume: 19
Number: 3
Identification Number: https://doi.org/10.18502/ijaai.v19i3.3454
ISSN: 1735-1502
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/3080

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