Chimeric antigen receptor (CAR)-modified T cell therapy evokes only modest antitumor responses in solid tumors. Meso-CAR-T cells are CAR-T cells targeted mesothelin, which are over-expressed in tumor tissues of breast cancer patients. To improve the therapeutic effects, we combined it with rAd.sT, a transforming growth factor β signaling-targeted oncolytic adenovirus, to therapy breast cancer. In subcutaneous MDA-MB-231 xenograft of NSG mice, both rAd.sT and meso-CAR-T inhibited tumor growth, however combination therapy produced stronger inhibitory effects. Interestingly, rAd.sT reduced tumor burden at initial stage following vector treatments, while meso-CAR-T cells decreased tumor burden at a later stage. Moreover, meso-CAR-T could target tumor microenvironments, and combination therapy could enhance cytokines production, such as interleukin (IL)-6 and IL-12 in tumor microenvironment. In conclusion, combination of rAd.sT with meso-CAR-T produced much more impressive antitumor responses to breast cancer and its metastasis, which could be developed as a promising therapeutic strategy.

中文翻译：

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靶向TGF-β的溶瘤腺病毒增强了间皮素靶向的嵌合抗原受体T细胞疗法对乳腺癌的抗肿瘤反应。

嵌合抗原受体（CAR）修饰的T细胞疗法在实体瘤中仅引起适度的抗肿瘤反应。Meso-CAR-T细胞是靶向间皮素的CAR-T细胞，在乳腺癌患者的肿瘤组织中过表达。为了提高治疗效果，我们将其与以转化生长因子β信号为靶点的溶瘤性腺病毒rAd.sT结合使用，以治疗乳腺癌。在NSG小鼠的皮下MDA-MB-231异种移植物中，rAd.sT和meso-CAR-T均抑制肿瘤生长，但是联合治疗产生更强的抑制作用。有趣的是，rAd.sT在载体治疗后的初始阶段降低了肿瘤负荷，而meso-CAR-T细胞在随后的阶段降低了肿瘤负荷。此外，介孔CAR-T可以靶向肿瘤微环境，联合治疗可以提高细胞因子的产生，例如肿瘤微环境中的白介素（IL）-6和IL-12。总之，rAd.sT与meso-CAR-T的结合对乳腺癌及其转移产生了更令人印象深刻的抗肿瘤反应，可以作为有前景的治疗策略进行开发。