MUC1 as a target for CAR-T therapy in head and neck squamous cell carinoma.
The modification of chimeric antigen receptor (CAR) endowing T cells with tumor-specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR-T therapy. The purpose of our study was to find and verify the potentials of CAR-T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non-neoplastic tissues (ANNT). Next, we constructed a second-generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth-generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR-T cells in vitro and in vivo, respectively. CAR-MUC1-IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR-T in the treatment of patients with HNSCC and provide evidence-based of MUC1 + CAR-T therapy.
['Mei|Zi|Z|', 'Zhang|Kai|K|', 'Lam|Alfred King-Yin|AK|', 'Huang|Junwen|J|', 'Qiu|Feng|F|', 'Qiao|Bin|B|0000-0002-9856-5864', 'Zhang|Yi|Y|0000-0001-9861-4681']
D000818:Animals D017209:Apoptosis D049109:Cell Proliferation D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D016219:Immunotherapy, Adoptive D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D018396:Mucin-1 D011379:Prognosis D000076962:Receptors, Chimeric Antigen D000077195:Squamous Cell Carcinoma of Head and Neck D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
MUC1 CAR-T head and neck squamous cell carcinoma IL22