Cancer Cell-targeted and Activatable Photoimmunotherapy Spares T Cells in a 3D Coculture Model
Cancer Cell-targeted and Activatable Photoimmunotherapy Spares T Cells in a 3D Coculture Model
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DOI：
10.1111/php.13153
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发表时间：
2020-03-01
影响因子：
3.3
通讯作者：
Spring, Bryan Q.
中科院分区：
文献类型：
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作者：
Kercher, Eric M.;Nath, Shubhankar;Spring, Bryan Q.
光动力疗法(PDT)是一种利用非电离近红外光激活内源性或外源性光敏剂(PSS)的光细胞毒作用的治疗方法。一个正在进行的癌症研究途径包括利用PDT刺激抗肿瘤免疫反应；然而，这些效应似乎在使用传统的、非特异性的PSS不能显著减少肿瘤的低剂量方案中诱导得最好。在较高的PDT剂量下，免疫增强的丧失可能部分是由于对局部免疫细胞群的不分青红皂白的破坏，包括肿瘤浸润性T细胞。我们之前介绍了使用分子靶向和细胞可激活的抗体-PS偶联物的肿瘤靶向可激活光免疫疗法(TAPIT)，以实现微尺度保真度的精确肿瘤光损伤。在这里，我们研究了Tapit在肿瘤免疫微环境的3D模型中提供的免疫细胞保护作用。我们报道，在上皮性卵巢癌细胞和T细胞的3D共培养模型中，高剂量Tapit节省了25%的局部免疫细胞群，是传统PDT方案的五倍。这些发现表明，Tapit的选择性增强可能被用来实现局部肿瘤减少，同时保留瘤内效应免疫细胞，否则如果用传统的PDT治疗，这些免疫细胞将会丢失。
Photodynamic therapy (PDT) is an established therapeutic modality that uses nonionizing near-infrared light to activate photocytotoxicity of endogenous or exogenous photosensitizers (PSs). An ongoing avenue of cancer research involves leveraging PDT to stimulate antitumor immune responses; however, these effects appear to be best elicited in low-dose regimens that do not provide significant tumor reduction using conventional, nonspecific PSs. The loss of immune enhancement at higher PDT doses may arise in part from indiscriminate damage to local immune cell populations, including tumor-infiltrating T cells. We previously introduced "tumor-targeted, activatable photoimmunotherapy" (taPIT) using molecular-targeted and cell-activatable antibody-PS conjugates to realize precision tumor photodamage with microscale fidelity. Here, we investigate the immune cell sparing effect provided by taPIT in a 3D model of the tumor immune microenvironment. We report that high-dose taPIT spares 25% of the local immune cell population, five times more than the conventional PDT regimen, in a 3D coculture model incorporating epithelial ovarian cancer cells and T cells. These findings suggest that the enhanced selectivity of taPIT may be utilized to achieve local tumor reduction with sparing of intratumor effector immune cells that would otherwise be lost if treated with conventional PDT.