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Information Journal Paper

Title

A VHH-Based Anti-MUC1 Chimeric Antigen Receptor for Specific Retargeting of Human Primary T Cells to MUC1-Positive Cancer Cells

Pages

  502-513

Abstract

 Objective: Immunotherapy with redirected T cells that express a chimeric antigen receptor (CAR) is a promising prospect in cancer treatment. Most CARs use murine-derived single-chain variable fragments (scFvs) as an antigen targeting moiety, which may lead to host immunogenic responses and engineered T cell disappearance. It seems that development of less immunogenic CARs, such as CARs composed of the camelid variable domain of heavy chain antibodies (VHHs) may likely overcome this obstacle. Here, we improved the expression of the VHH-based anti-MUC1 CAR gene construct using a third generation lentiviral vector in primary human T cells and assessed its effect on antigen specific targeting, activation and cytotoxicity of redirected human T cells. Materials and Methods: In this experimental study, we established a second generation novel CAR (VHH-based anti-MUC1 CAR) that contained a camelid-derived anti-MUC1 VHH followed by an IgG3 hinge, a CD28 transmembrane domain and signalling endodomains of CD28 and CD3ζ . Next, we constructed lentiviral vectors that contained this CAR gene construct using an optimized transiently virus production method and transduced it into human T cells. Cell surface expression of CAR, cytokine secretion and cytotoxic activity were assessed in the transduced CD3+ T cells. Results: The transduced T cells had high levels of surface expression of CAR. T cells that expressed anti-MUC1 CAR showed significantly increased secretion of Th1 cytokines, including IL-2, TNF alpha and IFN-γ , as well as cytotoxic activity upon recognition of MUC1 on tumour cells after co-incubation with T47D or MCF-7 (MUC1-positive) compared with A431 (MUC1-negative) or untransduced T cells. Conclusion: Our results suggested that, given the unique properties of VHHs to prevent immunogenic responses and tonic signalling, our novel VHH-based anti-MUC1 CAR might be effective for clinical purposes in cancer Immunotherapy.

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    Cite

    APA: Copy

    Rajabzadeh, Alireza, RAHBARIZADEH, FATEMEH, AHMADVAND, DAVOUD, KABIR SALMANI, MARYAM, & HAMIDIEH, AMIR ALI. (2021). A VHH-Based Anti-MUC1 Chimeric Antigen Receptor for Specific Retargeting of Human Primary T Cells to MUC1-Positive Cancer Cells. CELL JOURNAL (YAKHTEH), 22(4 (88)), 502-513. SID. https://sid.ir/paper/742508/en

    Vancouver: Copy

    Rajabzadeh Alireza, RAHBARIZADEH FATEMEH, AHMADVAND DAVOUD, KABIR SALMANI MARYAM, HAMIDIEH AMIR ALI. A VHH-Based Anti-MUC1 Chimeric Antigen Receptor for Specific Retargeting of Human Primary T Cells to MUC1-Positive Cancer Cells. CELL JOURNAL (YAKHTEH)[Internet]. 2021;22(4 (88)):502-513. Available from: https://sid.ir/paper/742508/en

    IEEE: Copy

    Alireza Rajabzadeh, FATEMEH RAHBARIZADEH, DAVOUD AHMADVAND, MARYAM KABIR SALMANI, and AMIR ALI HAMIDIEH, “A VHH-Based Anti-MUC1 Chimeric Antigen Receptor for Specific Retargeting of Human Primary T Cells to MUC1-Positive Cancer Cells,” CELL JOURNAL (YAKHTEH), vol. 22, no. 4 (88), pp. 502–513, 2021, [Online]. Available: https://sid.ir/paper/742508/en

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