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Nectin4-targeted VHH CAR T cells demonstrate potency against bladder cancer
Announcing a new article publication for Bio-Integration magazine. Bladder cancer (BLCA) is one of the most common malignancies and the second most common genitourinary tract tumor. Cell and gene therapy, which offer many advantages in the treatment of BLCA, are urgently needed. However, there is an important limitation of the currently reported single chain antibody chimeric antigen receptor targeting domain. Specifically, autoaggregation results in CAR-T depletion, which may originate from the linker peptide and folding stability between the variable domains (VH and VL) of the auto single-chain antibody. Humanized, small size, strong affinity single domain antibodies (variable domain heavy chain antibodies [VHH]) derived from camelids are promising alternatives. …
Nectin4-targeted VHH CAR T cells demonstrate potency against bladder cancer
Announcing a new article publication forOrganic integrationMagazine. Bladder cancer (BLCA) is one of the most common malignancies and the second most common genitourinary tract tumor. Cell and gene therapy, which offer many advantages in the treatment of BLCA, are urgently needed. However, there is an important limitation of the currently reported single chain antibody chimeric antigen receptor targeting domain. Specifically, autoaggregation results in CAR-T depletion, which may originate from the linker peptide and folding stability between the variable domains (VH and VL) of the auto single-chain antibody. Humanized, small size, strong affinity single domain antibodies (variable domain heavy chain antibodies [VHH]) derived from camelids are promising alternatives.
The second-generation nectin4-targeted VHH-CAR-T cells were constructed and the specific killing efficacy against BLCA cells was determinedin vitro. VHH-Nectin4-Car lentivirus was transduced into human T cells and CAR T cell phenotypes were analyzed by flow cytometry. Cell killing efficacy was evaluated using Nectin4-positive BLCA cells (SW780 and RT4) and Nectin4-negative U87-Mg cells as controls using the Xcelligence real-time cell analysis system. Expression of cytokine secretion (IFN-γ and IL-2) was measured by enzyme-linked immunosorbent assay.
Vhhnectin4-Car lentivirus treatment increased the proportion of CD4+ T and memory T cells. VHHNECTIN4-CAR-T cells had increased specific killing ability compared to control with VH-VL-based CAR-T cells, specifically recognized Nectin4+ BLCA cells, secreted cytokines and mediated cell apoptosis. Furthermore, Vhhnectin4-CAR-T had no effect on Nectin4-U87-mg cell growth.
VHHNECTIN4-CAR-T cells were produced with potent killing ability that specifically recognized Nectin4+ BLCA cellsin vitro.
Sources:
Niu, J.,et al.(2025). Novel CAR-T Cells Specifically Targeting Nectin4 Exhibit Effective Anti-Tumor Efficacy in Bladder Cancer Cell Lines. ORGANIC integration. doi.org/10.15212/bioi-2025-0041.