Laboratory of Veterinary Pathology, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Innovation and Core Technology Management, Olympus Corporation, Tokyo, Japan.
Cancer Med. 2023 Feb;12(4):4579-4589. doi: 10.1002/cam4.5302. Epub 2022 Oct 18.
Near-infrared photoimmunotherapy (NIR-PIT) is a novel form of cancer treatment using conjugates of antibody against overexpressed antigens in cancers and photoabsorber IRDye700DX. HER2 is overexpressed in various cancers, for which molecular targeted therapy such as trastuzumab has been developed. The present study investigated the efficacy potential of HER2-targeted NIR-PIT using trastuzumab-IRDye700DX conjugate (Tra-IR700) in HER2-positive breast cancer. We first examined the reactivity of Tra-IR700 and the cytotoxicity of NIR-PIT in vitro. HER2-positive BT-474 and SK-BR-3 cells and HER2-negative BT-20 cells were used. Tra-IR700 fluorescence was only observed in HER2-positive breast cancer cell lines, and the fluorescence was localized to the cell surface. Furthermore, HER2-positive breast cancer cell lines treated with NIR-PIT showed swelling and blebbing shortly after irradiation, and eventually increased PI-positive dead cells. Next, tumor accumulation of Tra-IR700 and tumor damage by NIR-PIT were examined in vivo. Tra-IR700 was administered intravenously to a xenograft model in which BT-474 cells were implanted subcutaneously in BALB/c nude mice. Tra-IR700 fluorescence was the highest in tumor tissue 1 day after administration, and the fluorescence was localized to the cell membrane of tumor cells. At this time point, NIR-PIT resulted in diffuse necrosis of tumor tissues 1 day after irradiation. These results suggest that NIR-PIT with Tra-IR700 induces a highly selective therapeutic effect in a HER2-positive breast cancer model. NIR-PIT using Tra-IR700 is expected to be a novel treatment for HER2-positive cancers, including breast cancer.
近红外光免疫治疗（NIR-PIT）是一种使用针对癌症中过表达抗原的抗体与光吸收剂 IRDye700DX 的偶联物治疗癌症的新方法。HER2 在各种癌症中过表达，为此已经开发了针对 HER2 的分子靶向治疗药物曲妥珠单抗。本研究使用针对 HER2 的近红外光免疫治疗剂曲妥珠单抗-IRDye700DX 偶联物（Tra-IR700），研究了其在 HER2 阳性乳腺癌中的疗效潜力。我们首先在体外检测了 Tra-IR700 的反应性和 NIR-PIT 的细胞毒性。使用了 HER2 阳性的 BT-474 和 SK-BR-3 细胞以及 HER2 阴性的 BT-20 细胞。Tra-IR700 荧光仅在 HER2 阳性乳腺癌细胞系中观察到，并且荧光定位于细胞表面。此外，HER2 阳性乳腺癌细胞系在接受 NIR-PIT 治疗后，在照射后不久即出现肿胀和起泡，最终增加了 PI 阳性的死亡细胞。接下来，在体内研究了 Tra-IR700 的肿瘤蓄积和 NIR-PIT 对肿瘤的损伤。将 Tra-IR700 静脉注射到皮下植入 BT-474 细胞的异种移植模型中。给药后 1 天，肿瘤组织中的 Tra-IR700 荧光最高，并且荧光定位于肿瘤细胞的细胞膜。此时，NIR-PIT 导致照射后 1 天肿瘤组织广泛坏死。这些结果表明，在 HER2 阳性乳腺癌模型中，Tra-IR700 的 NIR-PIT 诱导了高度选择性的治疗效果。使用 Tra-IR700 的 NIR-PIT 有望成为包括乳腺癌在内的 HER2 阳性癌症的新型治疗方法。
