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在顺铂和曲尼司特为基础的原创型 Pt(iv)前药 Traniplatin 处理的患者来源肿瘤外植体中,免疫细胞浸润增加。

Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast.

机构信息

Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, Barcelona, E-08028, Spain.

出版信息

Chem Commun (Camb). 2018 Jul 24;54(60):8324-8327. doi: 10.1039/c8cc02071j.

Abstract

Elevated intra-tumoral immune infiltrate is associated with an improved prognosis in cancer of distinct origins. Traniplatin (TPT) is a novel platinum(iv) pro-drug based on Cisplatin (CDDP) and the marketed drug Tranilast. When compared in vitro to Cisplatin, TPT showed increased cytotoxic activity against colon and lung cancer cells but decreased activity against immune cells. In addition, TPT efficiency was evaluated in tumor explants derived from colorectal cancer samples from patients subjected to intended curative surgery. TPT induced strong intra-tumoral cytotoxic activity yet was associated with an elevated presence of immune cell infiltrate, suggesting a reduced cytotoxic activity against immune cells in colorectal cancer.

摘要

肿瘤内免疫浸润增加与不同来源癌症的预后改善相关。曲奈普拉汀(TPT)是一种新型基于顺铂(CDDP)的铂(IV)前药,也是一种已上市的曲尼司特药物。与顺铂相比,TPT 在体外对结肠癌和肺癌细胞表现出更高的细胞毒性活性,但对免疫细胞的活性降低。此外,还评估了 TPT 在接受根治性手术的结直肠癌患者样本来源的肿瘤标本中诱导的活性。TPT 诱导了强烈的肿瘤内细胞毒性活性,但与免疫细胞浸润的增加相关,这表明在结直肠癌中对免疫细胞的细胞毒性活性降低。

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