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

• DOI: 10.22074/cellj.2021.6917
• Publication Date: 2021-01-01
• Authors: Alireza Rajabzadeh; Fatemeh Rahbarizadeh; Davoud Ahmadvand; M Kabir Salmani; Amir Ali Hamidieh
• Keywords: Cancer Immunotherapy; MUC1

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