PD-L1 near Infrared Photoimmunotherapy of Ovarian Cancer Model.

PD-L1 near Infrared Photoimmunotherapy of Ovarian Cancer Model.
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卵巢癌模型的程序性死亡配体1(PD-L1)近红外光免疫疗法

DOI:
10.3390/cancers14030619
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发表时间:
2022-01-26
期刊:
影响因子:
5.2
通讯作者:
Penet MF
Penet MF
中科院分区:
医学2区
文献类型:
--
作者:
Jin J;Sivakumar I;Mironchik Y;Krishnamachary B;Wildes F;Barnett JD;Hung CF;Nimmagadda S;Kobayashi H;Bhujwalla ZM;Penet MF

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卵巢癌是美国女性癌症相关死亡的主要原因之一。尽管治疗方法的改进延长了中位生存期,但晚期疾病患者的总体存活率并未发生显著变化。使用与近红外(NIR)染料偶联的抗体的光免疫疗法(PIT)构成了一种有效的治疗策略,用于检测和选择性地消除细胞群。程序性死亡-1(PD-1)/程序性死亡配体-1(PD-L1)信号通路被广泛研究用于免疫检查点阻断。PD-L1在所有主要的卵巢癌组织亚型中都有表达,通常由癌细胞和肿瘤相关巨噬细胞(TAMs)表达。在这里,我们使用NIR-PIT来消除卵巢癌移植瘤中表达PD-L1的TAMs和癌细胞。总体而言,我们的发现支持使用NIR-PIT作为卵巢癌的潜在治疗选择。(1)背景:尽管在手术方法和药物开发方面取得了进展,但卵巢癌仍然是妇科恶性肿瘤的主要死亡原因。被诊断为晚期疾病的患者接受积极的手术切除和化疗,但治疗后经常观察到耐药疾病的复发。晚期卵巢癌迫切需要有效的治疗方法。光免疫疗法(PIT),使用与近红外(NIR)染料结合的抗体,构成了一种有效的治疗策略,以检测和选择性地消除目标细胞群。(2)方法:在同基因小鼠卵巢癌模型中,我们利用近红外光谱分析技术靶向程序死亡配体1(PD-L1)。在体外培养的RAW264.7巨噬细胞和ID8-Defb29-VEGF细胞中检测PD-L1 PIT介导的细胞毒作用,并与ID8-Defb29-VEGF原位肿瘤进行比较。(3)结果:在体内外均观察到治疗效果。(4)结论:我们的数据强调了进一步研究的必要性,以评估使用近红外PIT治疗卵巢癌以改善卵巢癌治疗结果的潜力。
Ovarian cancer is one of the leading causes of cancer-related death among women in the United States. Overall survival of patients with advanced stage disease has not significantly changed despite improvements in treatment that have extended median survival. Photoimmunotherapy (PIT) using an antibody conjugated to a near infrared (NIR) dye constitutes an effective theranostic strategy to detect and selectively eliminate cell populations. The programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway is being extensively studied for immune checkpoint blockade. PD-L1 expression has been described across all major ovarian cancer histological subtypes and is commonly expressed by cancer cells and by tumor-associated macrophages (TAMs). Here, we used NIR-PIT to eliminate PD-L1-expressing TAMs and cancer cells in ovarian cancer xenografts. Overall, our findings support using NIR-PIT as a potential therapeutic option for ovarian cancer. (1) Background: Despite advances in surgical approaches and drug development, ovarian cancer is still a leading cause of death from gynecological malignancies. Patients diagnosed with late-stage disease are treated with aggressive surgical resection and chemotherapy, but recurrence with resistant disease is often observed following treatment. There is a critical need for effective therapy for late-stage ovarian cancer. Photoimmunotherapy (PIT), using an antibody conjugated to a near infrared (NIR) dye, constitutes an effective theranostic strategy to detect and selectively eliminate targeted cell populations. (2) Methods: Here, we are targeting program death ligand 1 (PD-L1) using NIR-PIT in a syngeneic mouse model of ovarian cancer. PD-L1 PIT-mediated cytotoxicity was quantified in RAW264.7 macrophages and ID8-Defb29-VEGF cells in culture, and in vivo with orthotopic ID8-Defb29-VEGF tumors. (3) Results: Treatment efficacy was observed both in vitro and in vivo. (4) Conclusions: Our data highlight the need for further investigations to assess the potential of using NIR-PIT for ovarian cancer therapy to improve the treatment outcome of ovarian cancer.
DOI: 10.1002/hed.26885
发表时间: 2021-12
影响因子: 2.9
作者:
Cognetti, David M.;Johnson, Jennifer M.;Curry, Joseph M.;Kochuparambil, Samith T.;McDonald, Darren;Mott, Frank;Fidler, Mary J.;Stenson, Kerstin;Vasan, Nilesh R.;Razaq, Mohammad A.;Campana, John;Ha, Patrick;Mann, Grace;Ishida, Kosuke;Garcia-Guzman, Miguel;Biel, Merrill;Gillenwater, Ann M.
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DOI: 10.1093/jnci/dji314
发表时间: 2005-10-19
影响因子: 10.3
作者:
del Carmen, MG;Rizvi, I;Hasan, T
通讯作者: Hasan, T
DOI: 10.1093/jnci/dju048
发表时间: 2014-05-14
影响因子: 10.3
作者:
Riester, Markus;Wei, Wei;Birrer, Michael J.
通讯作者: Birrer, Michael J.
DOI: 10.1158/0008-5472.can-20-2673
发表时间: 2021-06-01
期刊: Cancer research
影响因子: 11.2
作者:
Kurebayashi Y;Olkowski CP;Lane KC;Vasalatiy OV;Xu BC;Okada R;Furusawa A;Choyke PL;Kobayashi H;Sato N
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DOI: 10.1093/carcin/21.4.585
发表时间: 2000-04-01
期刊: CARCINOGENESIS
影响因子: 4.7
作者:
Roby, KF;Taylor, CC;Terranova, PF
通讯作者: Terranova, PF