Background/Objectives: Bladder cancer is a malignant disease that causes more than 199,922 deaths a year globally, in which ~75% of all newly diagnosed cases are non-muscle-invasive bladder cancer (NMIBC). Despite a number of treatments available, most NMIBC patients with high-grade tumors eventually recur. To add a novel therapy to complement the deficits of the current treatments, this study assesses the antitumor activity and mechanisms of action of intravesical xenogeneic urothelial cell (XUC) treatment as monotherapy and in combination with either chemotherapy or immune checkpoint inhibition (ICI).Methods: The orthotopic NMIBC graft tumor-bearing mice were randomly assigned into different treatment groups, receiving either intravesical XUCs, gemcitabine, anti-programmed death-ligand 1 (PD-L1) antibodies alone or in combination with gemcitabine or anti-PD-1 antibodies. The tumor responses, survival, and immune reactions were analyzed.Results: Intravesical XUC treatment exhibited significantly more antitumor activity to delay tumor progression than the control group and a similar effect to chemotherapy and ICI. In addition, there were significantly higher effects in the combined groups than single treatments. Immune tumor microenvironment and immune cell proliferation, cytotoxicity, and cytokine secretion were also activated by XUC treatment. Moreover, the combined groups have the highest effects.Conclusions: In vivo and ex vivo studies showed increased antitumor efficacy and immune responses by intravesical XUC treatment in single and combined treatments, suggesting a potential utility of this xenogeneic cell immunotherapeutic agent. Intravesical XUC treatment has the potential to address the substantial unmet need in NMIBC therapy as a bladder-sparing treatment option for NMIBC.
背景/目的：膀胱癌是一种全球每年导致超过199,922例死亡的恶性疾病，其中约75%的新诊断病例为非肌层浸润性膀胱癌（NMIBC）。尽管现有多种治疗方法，但大多数患有高级别肿瘤的NMIBC患者最终仍会复发。为补充现有治疗的不足并引入新型疗法，本研究评估了膀胱内灌注异种尿路上皮细胞（XUC）作为单药治疗以及与化疗或免疫检查点抑制剂（ICI）联合应用的抗肿瘤活性及其作用机制。 方法：将原位NMIBC移植瘤小鼠随机分配至不同治疗组，分别接受膀胱内XUC灌注、吉西他滨、抗程序性死亡配体1（PD-L1）抗体单药治疗，或与吉西他滨或抗PD-1抗体联合治疗。分析肿瘤反应、生存情况及免疫反应。 结果：膀胱内XUC治疗在延缓肿瘤进展方面表现出显著优于对照组的抗肿瘤活性，其效果与化疗及ICI相当。此外，联合治疗组的效果显著优于单一治疗。XUC治疗还能激活肿瘤免疫微环境及免疫细胞的增殖、细胞毒性和细胞因子分泌，且联合治疗组的效果最为显著。 结论：体内外研究表明，膀胱内XUC单药及联合治疗均能增强抗肿瘤疗效和免疫反应，提示这种异种细胞免疫治疗剂具有潜在应用价值。膀胱内XUC治疗有望作为NMIBC的保膀胱治疗选择，满足当前NMIBC治疗中尚未满足的重大临床需求。
肿瘤(癌症)患者之家