Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy that directly kills cancer cells as well as producing a therapeutic host immune response. Conventional immunotherapies, such as immune-activating cytokine therapy, checkpoint inhibition, engineered T cells and suppressor cell depletion, do not directly destroy cancer cells, but rely exclusively on activating the immune system. NIR-PIT selectively destroys cancer cells, leading to immunogenic cell death that initiates local immune reactions to released cancer antigens from dying cancer cells. These are characterized by rapid maturation of dendritic cells and priming of multi-clonal cancer-specific cytotoxic T cells that kill cells that escaped the initial direct effects of NIR-PIT. The NIR-PIT can be applied to a wide variety of cancers either as monotherapy or in combination with conventional immune therapies to further activate anti-cancer immunity. A global Phase 3 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03769506) of NIR-PIT targeting the epidermal growth factor receptor (EGFR) in patients with recurrent head and neck cancer is underway, employing RM1929/ASP1929, a conjugate of anti-EGFR antibody (cetuximab) plus the photo-absorber IRDye700DX (IR700). NIR-PIT has been given fast-track recognition by regulators in the USA and Japan. A variety of imaging methods, including direct IR700 fluorescence imaging, can be used to monitor NIR-PIT. As experience with NIR-PIT grows, additional antibodies will be employed to target additional antigens on other cancers or to target immune-suppressor cells to enhance host immunity. NIR-PIT will be particularly important in patients with localized and locally advanced cancers and may help such patients avoid side-effects associated with surgery, radiation and chemotherapy.

中文翻译：

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癌症的近红外光免疫疗法：一种杀死癌细胞并增强抗癌宿主免疫力的新方法。

摘要

近红外光免疫疗法 (NIR-PIT) 是最近开发的一种混合癌症疗法，可直接杀死癌细胞并产生治疗性宿主免疫反应。传统的免疫疗法，例如免疫激活细胞因子疗法、检查点抑制、工程 T 细胞和抑制细胞耗竭，并不直接破坏癌细胞，而是完全依赖于激活免疫系统。NIR-PIT 选择性地破坏癌细胞，导致免疫原性细胞死亡，从而引发局部免疫反应，以从垂死的癌细胞中释放癌症抗原。它们的特点是树突状细胞的快速成熟和多克隆癌症特异性细胞毒性 T 细胞的启动，这些细胞杀死逃避 NIR-PIT 最初直接影响的细胞。NIR-PIT 可作为单一疗法或与常规免疫疗法联合应用于多种癌症，以进一步激活抗癌免疫。一项针对复发性头颈癌患者表皮生长因子受体 (EGFR) 的 NIR-PIT 的全球 3 期临床试验 (https://clinicaltrials.gov/ct2/show/NCT03769506) 正在进行中，使用 RM1929/ASP1929，抗EGFR抗体（西妥昔单抗）加光吸收剂IRDye700DX（IR700）的偶联物。NIR-PIT 已获得美国和日本监管机构的快速认可。多种成像方法，包括直接 IR700 荧光成像，可用于监测 NIR-PIT。随着 NIR-PIT 经验的增长，额外的抗体将用于靶向其他癌症的额外抗原或靶向免疫抑制细胞以增强宿主免疫力。NIR-PIT 对于局部和局部晚期癌症患者尤其重要，可以帮助这些患者避免与手术、放射和化学疗法相关的副作用。