Prediction and Treatment for Cancer Immunotherapy Induced Myocarditis

癌症免疫治疗引起的心肌炎的预测和治疗

基本信息

  • 批准号:
    10217416
  • 负责人:
  • 金额:
    $ 18.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-05-01 至 2022-01-31
  • 项目状态:
    已结题

项目摘要

Abstract In the past 10 years, the FDA has approved 6 checkpoint inhibitors and quickly expanded indications from melanoma and non-small cell lung cancer to Hodgkin lymphoma, kidney, and bladder cancer. Moreover, there are more than 150 ongoing clinical trials on PD-1 inhibitors treatment alone. Despite the anti-cancer benefits, immunotherapy associated immune related adverse events affect a broad spectrum of organs, including heart. Current diagnosis in clinical practices are troponin test and electrocardiograms, which, however, lack of necessary sensitivity and specificity to myocarditis. Accordingly, in Specific Aim 1, we seek to identify transcriptomic (RNAseq/MirSeq) biomarkers that may have predictive value for checkpoint inhibitor treatment induced myocarditis. In this specific aim, we will be focused on patients who have developed autoimmune myocarditis after receiving checkpoint inhibitor treatments and have blood samples banked. Such patients provided an opportunity to identify new associative and predictive biomarkers that can serve as guideposts for the implementation of new therapeutic approaches to suppress the inflammatory drivers of cardiotoxicity. For medical management of immune Checkpoint Inhibitors associated myocarditis, current practices of subscribing steroids expose patients to immune suppression systemically. In Specific Aim 2, we will evaluate a new anti- inflammatory peptide-based nanoparticle system for delivering siRNA against NF-κB to manage myocarditis induced by immune checkpoint inhibitors. Different from currently existing approaches, the new technology proposed in Specific Aim 2 would enable anti-inflammation treatment delivery only to inflamed region in the heart. Moreover, the testing agent has known anti-cancer effects. Therefore, the success of Specific Aim 2 could provide precision treatment delivery and minimize systemic off-target side effects.
摘要 在过去的10年里,FDA已经批准了6种检查点抑制剂,并迅速扩大了适应症, 黑色素瘤和非小细胞肺癌到霍奇金淋巴瘤、肾癌和膀胱癌。而且 目前有超过150项关于PD-1抑制剂治疗的临床试验正在进行中。尽管有抗癌的好处, 免疫治疗相关免疫相关不良事件影响包括心脏在内的广泛器官。 目前临床实践中的诊断是肌钙蛋白测试和心电图,然而,缺乏 对心肌炎的敏感性和特异性。因此,在具体目标1中,我们寻求确定 可能对检查点抑制剂治疗具有预测价值的转录组学(RNAseq/MirSeq)生物标志物 诱发心肌炎。在这一特定目标中,我们将重点关注患有自身免疫性疾病的患者, 心肌炎后接受检查点抑制剂治疗,并有血液样本库。此类患者 提供了一个机会,以确定新的关联和预测生物标志物,可以作为路标, 实施新的治疗方法来抑制心脏毒性的炎症驱动因素。为 免疫检查点抑制剂相关性心肌炎的医疗管理, 类固醇使患者全身性地受到免疫抑制。在具体目标2中,我们将评估一种新的抗- 用于递送针对NF-κB siRNA以控制心肌炎的基于炎性肽的纳米颗粒系统 由免疫检查点抑制剂诱导。与现有的方法不同,新技术 具体目标2中提出的方法将使抗炎治疗仅针对心脏的炎症区域进行。 此外,测试剂具有已知的抗癌作用。因此,《特定目标2》的成功可能会 提供精确的治疗输送,并最大限度地减少全身脱靶副作用。

项目成果

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Hua Pan其他文献

Hua Pan的其他文献

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{{ truncateString('Hua Pan', 18)}}的其他基金

Prediction and Treatment for Cancer Immunotherapy Induced Myocarditis
癌症免疫治疗引起的心肌炎的预测和治疗
  • 批准号:
    10645593
  • 财政年份:
    2022
  • 资助金额:
    $ 18.69万
  • 项目类别:
Mitigate cisplatin induced acute kidney injury through preservation of vasculature and proximal tubule
通过保护脉管系统和近端小管减轻顺铂引起的急性肾损伤
  • 批准号:
    10644372
  • 财政年份:
    2021
  • 资助金额:
    $ 18.69万
  • 项目类别:
Mitigate cisplatin induced acute kidney injury through preservation of vasculature and proximal tubule
通过保护脉管系统和近端小管减轻顺铂引起的急性肾损伤
  • 批准号:
    10661849
  • 财政年份:
    2021
  • 资助金额:
    $ 18.69万
  • 项目类别:
Mitigate cisplatin induced acute kidney injury through preservation of vasculature and proximal tubule
通过保护脉管系统和近端小管减轻顺铂引起的急性肾损伤
  • 批准号:
    10209816
  • 财政年份:
    2021
  • 资助金额:
    $ 18.69万
  • 项目类别:

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