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Combined CD44- and CD25-targeted Near-Infrared Photoimmunotherapy Selectively Kills Cancer and Regulatory T cells in Syngeneic Mouse Cancer Models.

在同基因小鼠癌症模型中,CD44 和 CD25-targeted 近红外光免疫疗法联合选择性杀伤癌症和调节性 T 细胞。

  • 影响因子:8.58
  • DOI:10.1158/2326-6066.CIR-19-0517
  • 作者列表:"Maruoka Y","Furusawa A","Okada R","Inagaki F","Fujimura D","Wakiyama H","Kato T","Nagaya T","Choyke PL","Kobayashi H
  • 发表时间:2020-01-17
Abstract

:Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a monoclonal antibody conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, anti-CD25-IR700-targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3+CD25+CD4+ regulatory T cells (Tregs), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44- and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removing FOXP3+CD25+CD4+ Tregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44- and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44/CD25 NIR-PIT also resulted in some complete remissions, whereas this was not achieved with either type of NIR-PIT alone. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.

摘要

: 近红外光免疫治疗 (NIR-PIT) 是一种新开发的选择性癌症治疗,可诱导坏死和免疫原性细胞死亡,并利用与光吸收剂染料 IR700DX 偶联的单克隆抗体, 由 NIR 光激活。尽管 CD44 是与耐药性相关的表面癌症标志物,但 anti-CD44-IR700 NIR-PIT 可抑制多种肿瘤类型的细胞生长并延长生存期。同时,anti-CD25-IR700-targeted NIR-PIT 已被报道实现 FOXP3 + CD25 + CD4 + 调节性 T 细胞 (Tregs) 的选择性和局部耗竭, 它们是肿瘤微环境 (TME) 中的原代免疫抑制细胞,导致局部抗肿瘤免疫激活。联合 NIR-PIT 与 CD44-和 CD25-targeted 药物具有直接消除肿瘤细胞的潜力,也可以通过从 TME 中去除 FOXP3 + CD25 + CD4 + Tregs 来放大免疫反应。我们研究了 CD44-targeted NIR-PIT 单独、 CD25-targeted NIR-PIT 单独以及 CD44-和 CD25-targeted NIR-PIT 联合在几种同基因肿瘤模型中的治疗效果差异,包括 MC38-luc, LL/2 和 moc1。在所有肿瘤模型中,与 CD44-targeted NIR-PIT 单独相比,联合 NIR-PIT 显示显著的肿瘤生长抑制和延长的生存,与 CD25-targeted NIR-PIT 单独相比,MC38-luc 和 LL/ 2 个肿瘤。联合 CD44/CD25 NIR-PIT 也导致了一些完全缓解,而这不是单独使用两种类型的 NIR-PIT 实现的。因此, 在 TME 中同时靶向癌症抗原和免疫抑制细胞的联合 NIR-PIT 可能比任何一种类型的 NIR-PIT 单独使用更有效,并且可能具有在治疗的肿瘤中诱导延长免疫反应的潜力。

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翻译标题与摘要 下载文献
影响因子:8.58
发表时间:2020-01-17
DOI:10.1158/2326-6066.CIR-19-0517
作者列表:["Maruoka Y","Furusawa A","Okada R","Inagaki F","Fujimura D","Wakiyama H","Kato T","Nagaya T","Choyke PL","Kobayashi H"]

METHODS::Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a monoclonal antibody conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, anti-CD25-IR700-targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3+CD25+CD4+ regulatory T cells (Tregs), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44- and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removing FOXP3+CD25+CD4+ Tregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44- and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44/CD25 NIR-PIT also resulted in some complete remissions, whereas this was not achieved with either type of NIR-PIT alone. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.

关键词: 暂无
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