Department of Urology, Stanford University School of Medicine, Stanford, California.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
Clin Cancer Res. 2019 Jun 15;25(12):3561-3571. doi: 10.1158/1078-0432.CCR-18-3267. Epub 2019 Mar 19.
Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated mAb and light energy. CD47 is an innate immune checkpoint widely expressed on bladder cancer cells, but absent from luminal normal urothelium. Targeting CD47 for NIR-PIT has the potential to selectively induce cancer cell death and minimize damage to normal urothelium.
The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investigated in human bladder cancer cell lines and primary human bladder cancer cells derived from fresh surgical samples. Phagocytosis assays were performed to evaluate macrophage activity after NIR-PIT. Anti-CD47-IR700 was administered to murine xenograft tumor models of human bladder cancer for molecular imaging and NIR-PIT.
Cytotoxicity in cell lines and primary bladder cancer cells significantly increased in a light-dose-dependent manner with CD47-targeted NIR-PIT. Phagocytosis of cancer cells significantly increased with NIR-PIT compared with antibody alone ( = 0.0002). fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour postinjection and was detectable for at least 14 days. After a single round of CD47-targeted NIR-PIT, treated animals showed significantly slower tumor growth compared with controls ( < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth ( = 0.0104) and improved survival compared with controls.
CD47-targeted NIR-PIT increased direct cancer cell death and phagocytosis resulting in inhibited tumor growth and improved survival in a murine xenograft model of human bladder cancer.
近红外光免疫治疗（NIR-PIT）是一种将光敏剂结合抗体与光能相结合的局部分子癌症治疗方法。CD47 广泛表达于膀胱癌细胞，但不存在于腔面正常尿路上皮中，是一种先天免疫检查点。针对 CD47 的 NIR-PIT 有可能选择性地诱导癌细胞死亡，并最大限度地减少对正常尿路上皮的损伤。
在人膀胱癌细胞系和源自新鲜手术样本的原代人膀胱癌细胞中，研究了抗 CD47-IR700 的 NIR-PIT 的细胞毒性作用。进行吞噬作用测定以评估 NIR-PIT 后巨噬细胞的活性。将抗 CD47-IR700 施用于人膀胱癌的鼠异种移植肿瘤模型，用于分子成像和 NIR-PIT。
细胞系和原代膀胱癌细胞中的细胞毒性在光剂量依赖性的方式下，随着 CD47 靶向的 NIR-PIT 而显著增加。与单独抗体相比，NIR-PIT 后癌细胞的吞噬作用明显增加（=0.0002）。注射后 24 小时，肿瘤中的抗 CD47-IR700 的荧光强度达到峰值，至少可检测到 14 天。与对照组相比，单次 CD47 靶向 NIR-PIT 治疗后，处理过的动物的肿瘤生长明显减慢（<0.0001）。重复的 CD47 靶向 NIR-PIT 治疗进一步减缓了肿瘤生长（=0.0104），并提高了生存率。
CD47 靶向的 NIR-PIT 通过增加直接的癌细胞死亡和吞噬作用，从而抑制了人膀胱癌的鼠异种移植模型中的肿瘤生长并改善了生存率。
