Near-infrared photoimmunotherapy targeting human-EGFR in a mouse tumor model simulating current and future clinical trials.
Near-infrared photoimmunotherapy targeting human-EGFR in a mouse tumor model simulating current and future clinical trials.
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DOI：
10.1016/j.ebiom.2021.103345
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发表时间：
2021-05
期刊：
影响因子：
11.1
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Okada R;Furusawa A;Vermeer DW;Inagaki F;Wakiyama H;Kato T;Nagaya T;Choyke PL;Spanos WC;Allen CT;Kobayashi H
近红外光免疫疗法（NIR-PIT）是一种使用抗体-光吸收剂（IRDye 700DX，IR 700）缀合物（APC）的癌症治疗，所述抗体-光吸收剂缀合物结合靶细胞并被NIR光活化，诱导快速坏死细胞死亡。靶向人表皮生长因子受体（hEGFR）的NIR-PIT已被证明可以破坏表达hEGFR的人肿瘤细胞，并在免疫缺陷小鼠模型中有效。NIR-PIT还可以靶向肿瘤微环境中的细胞，例如，靶向CD 25的NIR-PIT可以用于选择性地耗尽肿瘤内的调节性T细胞（TcR）。本研究的目的是评价hEGFR和CD 25靶向NIR-PIT在新建立的表达hEGFR的鼠口咽细胞系（mEERL-hEGFR）中的联合治疗疗效。与IR 700偶联的帕尼单抗（pan-IR 700）用作NIR-PIT的癌细胞定向组分，抗CD 25-F（ab′）2-IR 700用作NIR-PIT的肿瘤微环境定向组分。使用四组荷瘤小鼠评价疗效：（1）非治疗组（对照），（2）基于pan-IR 700的NIR-PIT（pan-PIT），（3）基于抗CD 25-F（ab′）2-IR 700的NIR-PIT（CD 25-PIT），（4）NIR-PIT与pan-IR 700和抗CD 25- F（ab′）2-IR 700的组合（组合PIT）。联合PIT组显示出对肿瘤生长的最大抑制。癌细胞的破坏可能导致免疫应答，该免疫应答通过肿瘤微环境中TdR的损失而放大。组合的hEGFR和CD 25靶向NIR-PIT是一种有希望的治疗hEGFR表达癌症的方法，其中Treg细胞发挥免疫抑制作用。
near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that uses antibody-photoabsorber (IRDye700DX, IR700) conjugates (APCs) which bind to target cells and are photoactivated by NIR light inducing rapid necrotic cell death. NIR-PIT targeting human epidermal growth factor receptor (hEGFR) has been shown to destroy hEGFR expressing human tumor cells and to be effective in immunodeficient mouse models. NIR-PIT can also be targeted to cells in the tumor microenvironment, for instance, CD25-targeted NIR-PIT can be used to selectively deplete regulatory T cells (Tregs) within a tumor. The aim of this study was to evaluate the combined therapeutic efficacy of hEGFR and CD25-targeted NIR-PIT in a newly established hEGFR expressing murine oropharyngeal cell line (mEERL-hEGFR). panitumumab conjugated with IR700 (pan-IR700) was used as the cancer cell-directed component of NIR-PIT and anti-CD25-F(ab′)2-IR700 was used as the tumor microenvironment-directed component of NIR-PIT. Efficacy was evaluated using tumor-bearing mice in four groups: (1) non-treatment group (control), (2) pan-IR700 based NIR-PIT (pan-PIT), (3) anti-CD25-F(ab′)2-IR700 based NIR-PIT (CD25-PIT), (4) combined NIR-PIT with pan-IR700 and anti-CD25- F(ab′)2-IR700 (combined PIT). the combined PIT group showed the greatest inhibition of tumor growth. Destruction of cancer cells likely leads to an immune response which is amplified by the loss of Tregs in the tumor microenvironment. combined hEGFR and CD25-targeted NIR-PIT is a promising treatment for hEGFR expressing cancers in which Treg cells play an immunosuppressive role.
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影响因子：
10.1
作者：
Nagaya T;Friedman J;Maruoka Y;Ogata F;Okuyama S;Clavijo PE;Choyke PL;Allen C;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
17.1
作者：
Sato K;Sato N;Xu B;Nakamura Y;Nagaya T;Choyke PL;Hasegawa Y;Kobayashi H
通讯作者：
Kobayashi H
DOI：
10.1158/1078-0432.ccr-11-0503
发表时间：
2011-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Klebanoff CA;Gattinoni L;Palmer DC;Muranski P;Ji Y;Hinrichs CS;Borman ZA;Kerkar SP;Scott CD;Finkelstein SE;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
6.6
作者：
Nagaya, Tadanobu;Nakamura, Yuko;Kobayashi, Hisataka
通讯作者：
Kobayashi, Hisataka
影响因子：
--
作者：
Nagaya T;Nakamura Y;Sato K;Zhang YF;Ni M;Choyke PL;Ho M;Kobayashi H
通讯作者：
Kobayashi H