Okada Ryuhei, Asakage Takahiro
Department of Head and Neck Surgery, Institute of Science Tokyo, Tokyo, Japan.
Jpn J Clin Oncol. 2025 May 4. doi: 10.1093/jjco/hyaf069.
Use of antibody-drug conjugates (ADCs) is rapidly increasing in the field of oncology. While ADCs exhibit strong and cell-selective cytotoxicity, they do not show spatial selectivity. Near-infrared photoimmunotherapy (NIR-PIT, Alluminox™) utilizes photoactivatable ADCs, that is, antibody-photoabsorber conjugates (APCs). The photoabsorber used in NIR-PIT, IRDye700DX (IR700), is activated by light of ~690 nm wavelength. APCs, usually administered by intravenous injection, bind to the target cell surface, and subsequent excitation-light illumination dramatically changes the status of IR700 from hydrophilic to hydrophobic, inducing aggregation of the APC-target molecule complex and cell burst. Dying cells release neoantigens as well as damage-associated molecular patterns, resulting in immunogenic cell death (ICD). Based on the favorable results of clinical trials, epidermal growth factor-targeted NIR-PIT has been performed in Japan since 2021 for patients with unresectable head and neck cancers (HNCs). Since pain and local edema are frequent adverse events (AEs), various measures have been taken against these AEs. Because NIR-PIT induces ICD, combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy is thought to be a rather effective strategy. NIR-PIT could also locally destroy immune suppressor cells, such as regulatory T cells, in the tumor microenvironment. Currently, numerous clinical trials are under way to evaluate the efficacy of NIR-PIT as well as of combined NIR-PIT plus ICI therapy. In this review article, we describe the basics of NIT-PIT, results of translational experiments, current clinical application of NIT-PIT in HNCs, and relevant ongoing clinical trials.
抗体药物偶联物（ADC）在肿瘤学领域的应用正在迅速增加。虽然ADC具有强大的细胞选择性细胞毒性，但它们不具有空间选择性。近红外光免疫疗法（NIR-PIT，Alluminox™）利用可光激活的ADC，即抗体-光吸收剂偶联物（APC）。NIR-PIT中使用的光吸收剂IRDye700DX（IR700）可被波长约为690 nm的光激活。APC通常通过静脉注射给药，与靶细胞表面结合，随后的激发光照射会使IR700的状态从亲水性急剧变为疏水性，导致APC-靶分子复合物聚集并使细胞破裂。垂死的细胞会释放新抗原以及损伤相关分子模式，从而导致免疫原性细胞死亡（ICD）。基于临床试验的良好结果，自2021年以来，日本已对不可切除的头颈癌（HNC）患者进行了表皮生长因子靶向的NIR-PIT治疗。由于疼痛和局部水肿是常见的不良事件（AE），因此已针对这些AE采取了各种措施。由于NIR-PIT诱导ICD，因此将NIR-PIT与免疫检查点抑制剂（ICI）疗法联合使用被认为是一种相当有效的策略。NIR-PIT还可以局部破坏肿瘤微环境中的免疫抑制细胞，如调节性T细胞。目前，正在进行大量临床试验以评估NIR-PIT以及NIR-PIT联合ICI疗法的疗效。在这篇综述文章中，我们描述了NIT-PIT的基础知识、转化实验结果、NIT-PIT在HNC中的当前临床应用以及相关的正在进行的临床试验。
