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V-set and immunoglobulin domain-containing protein 1 (VSIG1), also known as Glycoprotein A34 or A34 antigen, is a type I transmembrane protein and a member of the junctional adhesion molecule (JAM) family within the immunoglobulin superfamily [1, 10]. It is characterized by a highly restricted expression pattern in normal tissues, primarily localized to the gastric mucosa and testicular germ cells [1, 2]. In the context of oncology, VSIG1 is significantly overexpressed in several malignancies, including gastric, esophageal, and ovarian cancers, which has led to its identification as a promising target for antibody-based immunotherapy and chimeric antigen receptor (CAR) T-cell therapy [1, 19, 23]. While its precise physiological role is still being elucidated, VSIG1 is involved in cell-cell adhesion and has been implicated in the regulation of the Wnt/beta-catenin signaling pathway and the prevention of metastasis in certain cancers [26, 29, 31]. Therapeutic development efforts focus on leveraging its tumor-specific overexpression to deliver cytotoxic agents or recruit immune cells to the tumor microenvironment, although the potential for off-target effects on normal stomach and testicular tissues remains a key safety consideration [1, 41].
Targeted immunotherapy including antibody-dependent cellular cytotoxicity (ADCC) and CAR-T cell-mediated cytotoxicity
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