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The Vascular Disrupting Agent CA4P Improves the Antitumor Efficacy of CAR-T Cells in Preclinical Models of Solid Human Tumors.
Molecular Therapy ( IF 12.4 ) Pub Date : 2019-10-18 , DOI: 10.1016/j.ymthe.2019.10.010 Changwen Deng 1 , Jingjing Zhao 1 , Shixin Zhou 1 , Jiebin Dong 1 , Jixiang Cao 1 , Junshuang Gao 1 , Yun Bai 1 , Hongkui Deng 2
Molecular Therapy ( IF 12.4 ) Pub Date : 2019-10-18 , DOI: 10.1016/j.ymthe.2019.10.010 Changwen Deng 1 , Jingjing Zhao 1 , Shixin Zhou 1 , Jiebin Dong 1 , Jixiang Cao 1 , Junshuang Gao 1 , Yun Bai 1 , Hongkui Deng 2
Affiliation
Chimeric antigen receptor (CAR) T cell therapy remains relatively ineffective against solid tumors due to inadequate infiltration and in vivo expansion of CAR-T cells. Unlike hematological malignancies, solid tumors have vascular barriers that hinder CAR-T cells from reaching the tumor site. Here, we demonstrated that combretastatin A-4 phosphate (CA4P), a vascular disrupting agent (VDA), can significantly improve the infiltration ability of CAR-T cells in solid tumors as evidenced by elevated levels of IFN-γ. Moreover, combined treatment with CA4P and CAR-T cells greatly increased the therapeutic efficiency of the CAR-T cells in subcutaneous ovarian cancer mouse xenograft models and patient-derived xenograft (PDX) models of colon and ovarian carcinoma. Our findings highlight CA4P as an effective antitumor agent candidate for combination with CAR-T cells in clinical applications to treat solid tumors.
中文翻译:
在实体人类肿瘤的临床前模型中,血管破坏剂CA4P可改善CAR-T细胞的抗肿瘤功效。
嵌合抗原受体(CAR)T细胞疗法由于对CAR-T细胞的浸润和体内扩增不足,对实体瘤仍然相对无效。与血液系统恶性肿瘤不同,实体瘤具有阻碍CAR-T细胞到达肿瘤部位的血管屏障。在这里,我们证明了康普他汀A-4磷酸酯(CA4P),一种血管破坏剂(VDA),可以显着提高实体瘤中CAR-T细胞的浸润能力,这可通过IFN-γ的升高来证明。此外,CA4P和CAR-T细胞的联合治疗大大提高了CAR-T细胞在结肠癌和卵巢癌的皮下卵巢癌小鼠异种移植模型以及患者源性异种移植(PDX)模型中的治疗效率。
更新日期:2019-10-19
中文翻译:
在实体人类肿瘤的临床前模型中,血管破坏剂CA4P可改善CAR-T细胞的抗肿瘤功效。
嵌合抗原受体(CAR)T细胞疗法由于对CAR-T细胞的浸润和体内扩增不足,对实体瘤仍然相对无效。与血液系统恶性肿瘤不同,实体瘤具有阻碍CAR-T细胞到达肿瘤部位的血管屏障。在这里,我们证明了康普他汀A-4磷酸酯(CA4P),一种血管破坏剂(VDA),可以显着提高实体瘤中CAR-T细胞的浸润能力,这可通过IFN-γ的升高来证明。此外,CA4P和CAR-T细胞的联合治疗大大提高了CAR-T细胞在结肠癌和卵巢癌的皮下卵巢癌小鼠异种移植模型以及患者源性异种移植(PDX)模型中的治疗效率。