PD1, programmed cell death protein 1

PD1 , 程序性细胞死亡蛋白 1
  • 文章类型: Journal Article
    肿瘤术后复发是导致治疗失败的主要原因。然而,复发的初始阶段不容易发现,后期很难治愈。为了提高术后患者的生活质量,开发了一种有效的协同免疫疗法,以实现对手术后肿瘤复发的早期诊断和治疗,同时。在本文中,制备了两种基于金纳米棒(AuNRs)平台的治疗剂。一种试剂中的AuNRs和量子点(QDs)用于检测癌胚抗原(CEA),使用荧光共振能量转移(FRET)技术来指示原位复发的发生,而另一种药物中的AuNRs用于光热治疗(PTT),与抗PDL1介导的免疫治疗一起缓解肿瘤转移的过程。一系列试验表明,这种协同免疫疗法可以诱导肿瘤细胞死亡和CD3+/CD4+T淋巴细胞和CD3+/CD8+T淋巴细胞的产生增加。此外,与单一免疫疗法相比,协同免疫疗法分泌的免疫因子(IL-2,IL-6和IFN-γ)更多.这种协同的免疫治疗策略可以同时用于肿瘤术后复发的诊断和治疗。为基础和临床研究提供了新的视角。
    Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of in situ recurrence, while AuNRs in the other agent was used for photothermal therapy (PTT), together with anti-PDL1 mediated immunotherapy to alleviate the process of tumor metastasis. A series of assays indicated that this synergistic immunotherapy could induce tumor cell death and the increased generation of CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Besides, more immune factors (IL-2, IL-6, and IFN-γ) produced by synergistic immunotherapy were secreted than mono-immunotherapy. This cooperative immunotherapy strategy could be utilized for diagnosis and treatment of postoperative tumor recurrence at the same time, providing a new perspective for basic and clinical research.
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  • 文章类型: Journal Article
    JS001(toripalimab)是一种人源化IgG单克隆抗体,其强烈抑制程序性细胞死亡蛋白1(PD1)。在这项研究中,我们使用不同的碘同种型(nat/124/125I)标记JS001探针以靶向人PD1(hPD1)抗原.体外,natI-JS001的半数最大有效浓度(EC50)值与JS001无显著差异。孵育2小时后,活化T细胞对125I-JS001的摄取是未活化T细胞的5.63倍。植物血凝素(PHA)刺激后125I-JS001对不同谱系T细胞的结合亲和力达到4.26nmol/L。对携带小鼠肉瘤S180细胞肿瘤的人源化PD1C57BL/6小鼠进行免疫-正电子发射断层扫描(免疫-PET)成像验证。病理染色用于评估肿瘤组织中PD1的表达。同源124I-人IgG(124I-hIgG)组或阻断组用作对照组。Immuno-PET成像显示,在人源化PD1小鼠模型中,124I-JS001组在不同时间点的肿瘤区域的摄取明显高于阻断组或124I-hIgG组。一起来看,这些结果表明,这种放射性示踪剂具有用于PD1阳性肿瘤的非侵入性监测和指导肿瘤特异性个性化免疫治疗的潜力.
    JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (nat/124/125I) to label JS001 probes to target the human PD1 (hPD1) antigen. In vitro, the half maximal effective concentration (EC50) value of natI-JS001 did not significantly differ from that of JS001. The uptake of 125I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of 125I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized PD1 C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous 124I-human IgG (124I-hIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the 124I-JS001 group at different time points was significantly higher than that of the blocking group or the 124I-hIgG group in the humanized PD1 mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.
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  • 文章类型: Journal Article
    随着生物治疗的发展,生物大分子药物最近获得了极大的关注,特别是在药物开发领域由于复杂的体内功能。在过去的几年里,已经开发了各种各样的生物大分子药物给药策略,以克服成药的困难,例如,不稳定,容易受到生理障碍的限制。应用新型递送系统递送生物大分子药物通常可以延长半衰期,增加生物利用度,或提高患者的依从性,大大提高了生物大分子药物的疗效和临床应用潜力。在这次审查中,总结了近年来关于高分子药物在癌症治疗中的药物递送策略的研究,主要是借鉴过去五年的发展。
    With the development of biotherapy, biomacromolecular drugs have gained tremendous attention recently, especially in drug development field due to the sophisticated functions in vivo. Over the past few years, a motley variety of drug delivery strategies have been developed for biomacromolecular drugs to overcome the difficulties in the druggability, e.g., the instability and easily restricted by physiologic barriers. The application of novel delivery systems to deliver biomacromolecular drugs can usually prolong the half-life, increase the bioavailability, or improve patient compliance, which greatly improves the efficacy and potentiality for clinical use of biomacromolecular drugs. In this review, recent studies regarding the drug delivery strategies for macromolecular drugs in cancer therapy are summarized, mainly drawing on the development over the last five years.
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