一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Inhaled dry powder cisplatin increases antitumour response to anti-PD1 in a murine lung cancer model.
Inhaled dry powder cisplatin increases antitumour response to anti-PD1 in a murine lung cancer model.
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尽管肺癌的靶向治疗和免疫治疗取得了进展,但化疗仍是大多数不同分期患者治疗的基石。吸入化疗是一种有前景的策略,可靶向肺部肿瘤并限制诱导的严重全身毒性。顺铂吸入干粉(CIS-DPI)作为一种通过肺部途径局部递送顺铂且全身毒性最小的创新方式进行了测试。在体内,CIS-DPI在M109原位小鼠肺肿瘤模型中表现出剂量依赖性的抗增殖活性,并上调了肺肿瘤细胞上的免疫检查点PD-L1。与免疫检查点抑制剂anti-PD1联合使用,CIS-DPI相比anti-PD1单药治疗显示出显著缩小的肿瘤体积、增加的反应者数量以及延长的中位生存期。此外,CIS-DPI与anti-PD1联合诱导了肿瘤内常规树突状细胞和TIL(肿瘤浸润淋巴细胞)的募集,突出了抗肿瘤免疫反应。本研究表明,将CIS-DPI与anti-PD1联合是一种改善肺癌治疗的有前景的策略。
Despite advances in targeted therapies and immunotherapy in lung cancer, chemotherapy remains the backbone of treatment in most patients at different stages of the disease. Inhaled chemotherapy is a promising strategy to target lung tumours and to limit the induced severe systemic toxicities. Cisplatin dry powder for inhalation (CIS-DPI) was tested as an innovative way to deliver cisplatin locally via the pulmonary route with minimal systemic toxicities.
In vivo, CIS-DPI demonstrated a dose-dependent antiproliferative activity in the M109 orthotopic murine lung tumour model and upregulated the immune checkpoint PD-L1 on lung tumour cells. Combination of CIS-DPI with the immune checkpoint inhibitor anti-PD1 showed significantly reduced tumour size, increased the number of responders and prolonged median survival over time in comparison to the anti-PD1 monotherapy.
Furthermore, the CIS-DPI and anti-PD1 combination induced an intra-tumour recruitment of conventional dendritic cells and tumour infiltrating lymphocytes, highlighting an anti-tumour immune response.
This study demonstrates that combining CIS-DPI with anti-PD1 is a promising strategy to improve lung cancer therapy.
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