Interleukin-15 after Near-Infrared Photoimmunotherapy (NIR-PIT) Enhances T Cell Response against Syngeneic Mouse Tumors.

Interleukin-15 after Near-Infrared Photoimmunotherapy (NIR-PIT) Enhances T Cell Response against Syngeneic Mouse Tumors.
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DOI:
10.3390/cancers12092575
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发表时间:
2020-09-10
期刊:
影响因子:
5.2
通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
医学2区
文献类型:
--
作者:
Maruoka Y;Furusawa A;Okada R;Inagaki F;Wakiyama H;Kato T;Nagaya T;Choyke PL;Kobayashi H

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近红外光免疫疗法是一种新开发的高选择性癌症治疗方法,它采用单克隆抗体与光吸收染料IRDye 700DX结合,可被690 nm光激活。靶向癌细胞的近红外光免疫疗法仅在靶癌细胞上选择性地诱导快速坏死/免疫原性细胞死亡,并且这诱导抗肿瘤宿主免疫,包括可与癌症特异性抗原反应的多慢性T细胞的再引发和增殖。白细胞介素-15是一种I型细胞因子,其激活自然杀伤细胞、B细胞和T细胞,同时对缺乏白细胞介素-15受体的调节性T细胞具有最小的影响。因此,白细胞介素-15给药结合癌细胞靶向近红外光免疫疗法可以通过增加抗肿瘤宿主免疫力来进一步抑制肿瘤生长。在接受这种联合治疗的荷瘤免疫活性小鼠中,与单独的单一治疗相比,证明了显著的肿瘤生长抑制和延长的存活期,并且在联合治疗的小鼠中肿瘤浸润性CD 8 + T细胞的数量增加。白细胞介素-15增强肿瘤靶向近红外光免疫治疗的疗效。近红外光免疫疗法(NIR-PIT)是一种新开发的高选择性癌症治疗方法,采用单克隆抗体(mAb)与光吸收染料IRDye 700DX结合,可被690 nm光激活。靶向癌细胞的NIR-PIT诱导快速坏死/免疫原性细胞死亡(ICD),其诱导抗肿瘤宿主免疫,包括T细胞的再引发和增殖。白细胞介素-15(IL-15)是一种细胞因子,其激活自然杀伤(NK)细胞、B细胞和T细胞,同时对缺乏IL-15受体的调节性T细胞(TCLs)具有最小的影响。在这里,我们假设IL-15与癌细胞靶向NIR-PIT一起施用可以通过增加抗肿瘤宿主免疫力来进一步抑制肿瘤生长。三种同基因小鼠肿瘤模型,MC 38-luc、LL/2和MOC 1,进行了CD 44靶向NIR-PIT和短期IL-15联合给药,并进行了适当的对照。与单药治疗相比,NIR-PIT后IL-15联合治疗可更有效地抑制荷瘤小鼠的肿瘤生长,延长生存期,并增加肿瘤浸润的CD 8 + T细胞。IL-15似乎增强了癌症靶向NIR-PIT的治疗效果。
Near infrared photoimmunotherapy is a newly developed and highly selective cancer treatment that employs a monoclonal antibody conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted near infrared photoimmunotherapy selectively induces rapid necrotic/immunogenic cell death only on target cancer cells and this induces antitumor host immunity including re-priming and proliferation of multi-chronal T-cells that can react with cancer-specific antigens. Interleukin-15 is a type-I cytokine that activates natural killer-, B- and T-cells while having minimal effect on regulatory T-cells that lack the interleukin-15 receptor. Therefore, interleukin-15 administration combined with cancer cell-targeted near infrared photoimmunotherapy could further inhibit tumor growth by increasing antitumor host immunity. In tumor-bearing immunocompetent mice receiving this combination therapy, significant tumor growth inhibition and prolonged survival was demonstrated compared with either single therapy alone, and tumor infiltrating CD8+ T-cells increased in number in combination-treated mice. Interleukin-15 enhances therapeutic effects of cancer-targeted near infrared photoimmunotherapy. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted NIR-PIT induces rapid necrotic/immunogenic cell death (ICD) that induces antitumor host immunity including re-priming and proliferation of T cells. Interleukin-15 (IL-15) is a cytokine that activates natural killer (NK)-, B- and T-cells while having minimal effect on regulatory T cells (Tregs) that lack the IL-15 receptor. Here, we hypothesized that IL-15 administration with cancer cell-targeted NIR-PIT could further inhibit tumor growth by increasing antitumor host immunity. Three syngeneic mouse tumor models, MC38-luc, LL/2, and MOC1, underwent combined CD44-targeted NIR-PIT and short-term IL-15 administration with appropriate controls. Comparing with the single-agent therapy, the combination therapy of IL-15 after NIR-PIT inhibited tumor growth, prolonged survival, and increased tumor infiltrating CD8+ T cells more efficiently in tumor-bearing mice. IL-15 appears to enhance the therapeutic effect of cancer-targeted NIR-PIT.
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