CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CD155-based chimeric antigen receptor T cells: a promising immunotherapy for cervical and breast cancer.
CD155-based chimeric antigen receptor T cells: a promising immunotherapy for cervical and breast cancer.
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我们的研究结果为基于 CD155 的 CAR-T 细胞疗法在宫颈癌和乳腺癌中的疗效和安全性提供了有力证据。本研究为越来越多支持 CD155 靶向免疫疗法在宫颈癌和乳腺癌患者中潜在临床应用的研究增添了证据。
作为一种在宫颈癌和乳腺癌中过表达的免疫检查点分子,CD155是嵌合抗原受体(CAR)T细胞治疗的一个有吸引力的靶点。然而,在考虑临床转化之前,在临床前模型中全面评估基于CD155的CAR-T 细胞的疗效和安全性至关重要。
在本研究中,我们开发了一种基于CD155的CAR,包含人TIGIT的胞外域、4-1BB和CD3z信号域,并利用宫颈癌和乳腺癌小鼠模型全面评估了基于CD155的CAR-T 细胞所引发的抗肿瘤反应。该CAR构建体经专门设计,用于识别并靶向表达CD155的肿瘤细胞。
我们的研究结果表明,CD155在大多数临床宫颈癌和乳腺癌组织中呈阳性染色,而在正常组织中呈无染色或低染色。此外,我们观察到CD155的表达水平与恶性肿瘤细胞的增殖之间存在相关性。基于CD155的CAR-T 细胞在体外能有效识别并清除表达CD155的肿瘤细胞。此外,使用宫颈癌和乳腺癌小鼠模型进行的体内实验显示,给予这些CAR-T 细胞可使已形成的肿瘤显著消退,且未引起任何可观察到的毒性。此外,清除CD155阳性肿瘤细胞能够有效消除具有高增殖率的肿瘤细胞。这表明该治疗方法可能为宫颈癌和乳腺癌患者提供一种安全有效的选择。
In this study, we developed a CD155-based CAR comprising the extracellular domain of the human TIGIT, 4-1BB, and CD3z signaling domains and utilized a murine model of cervical and breast cancer to comprehensively evaluate the antitumor responses elicited by the CD155-based CAR T cells. The CAR construct was specifically designed to recognize and target CD155-expressing tumor cells.
The results of our study indicated that CD155 exhibits positive staining in the majority of clinical cervical and breast cancer tissues while showing no or low staining in normal tissues. In addition, we observed a correlation between the expression level of CD155 and the proliferation of malignant tumor cells. CD155-based CAR T cells effectively recognize and eliminate CD155-expressing tumor cells in vitro . Moreover, in vivo experiments using a murine model of cervical and breast cancer revealed that the administration of these CAR T cells leads to significant regression of established tumors without causing any observable toxicity. In addition, the clearance of CD155-positive tumor cells can effectively eliminate tumor cells that exhibit high proliferation rates. This suggests that the treatment approach may offer a safe and effective option for patients with cervical and breast cancer. DISCUSSION: Overall, our findings provide strong evidence for the efficacy and safety of CD155-based CAR T-cell therapy in cervical and breast cancer. This study contributes to the growing body of research supporting the potential clinical application of CD155-targeted immunotherapy for patients with cervical and breast cancer.
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