肿瘤细胞治疗研究
英文原题：Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.
为解决CAR-T疗法中实体瘤靶向的难题，我们利用了A56抗原，该抗原在全身给予溶瘤痘苗病毒（OVV）后，独特地表达于多种癌细胞上。
为解决CAR-T疗法中实体瘤靶向的难题，我们利用了A56抗原，该抗原在全身给予溶瘤痘苗病毒（OVV）后独特地表达于多种癌细胞上。免疫组化检测精确证实了A56仅定位于肿瘤组织。体外研究显示，A56依赖性CAR-T细胞毒性在多种癌细胞系中具有明显优势。基于这些体外观察结果，我们在荷HCT-116肿瘤的非肥胖糖尿病/重度联合免疫缺陷（NOD/SCID）小鼠中策略性地联合给予A56 CAR-T细胞、OVV和羟基脲（HU），导致肿瘤体积显著缩小并延长了进展时间。因此，靶向A56的组合免疫疗法具有减少CAR-T对正常细胞意外效应同时保持其抗癌细胞有效性的优势。此外，我们通过OVV在肿瘤上植入A56的方法促进了CAR-T细胞在各种实体瘤中的广泛治疗应用。
To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.
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