Tumor-expressed immune checkpoint B7x-mediated resistance to anti-CTLA-4 therapy.

肿瘤表达的免疫检查点 B7x 介导的抗 CTLA-4 治疗耐药性。

基本信息

批准号：
10429780
负责人：
Xingxing Zang
金额：
$ 37.8万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10429780
关键词：
Address Ants Basic Science Biology Bladder Brain Breast CD276 gene CD28 gene CD80 gene CTLA4 blockade CTLA4 gene Cancer Patient Cell physiology Cell surface Chromatin Clinical Clinical Research Combined Modality Therapy Data Disease Progression Esophagus Family Gallbladder Generations Goals Human Immune Immunosuppression Immunotherapy In Vitro Kidney Liver Location Lung Malignant Neoplasms Mediating Mission Outcome Ovary PD-1/PD-L1 Pancreas Pathway interactions Pharmaceutical Preparations Phylogenetic Analysis Prostate Proteins Public Health Publishing Regulatory T-Lymphocyte Research Resistance Skin Stomach T-Lymphocyte Testing Therapeutic Therapeutic Studies Thyroid Gland Translating Treatment Efficacy Trees United States National Institutes of Health VTCN1 gene Validation anti-CTLA-4 therapy anti-CTLA4 base bone cancer drug resistance cancer immunotherapy cancer therapy cancer transplantation genome-wide immune checkpoint immune checkpoint blockade in vivo innovation insight macrophage member mouse model neoplastic cell novel novel therapeutics overexpression pre-clinical programmed cell death ligand 1 programmed cell death protein 1 programs receptor receptor expression tool transcriptome tumor

项目摘要

Tumor-expressed immune checkpoint B7x-mediated resistance to anti-CTLA-4 therapy Immune checkpoint blockade of CTLA-4 and PD-1/PD-L1 have advanced the treatment of cancer patients. However, one of the biggest challenges is that the majority of cancer patients do not respond to these treatments. Based on our new results, our central hypothesis of this proposed revision research is that tumor-expressed immune checkpoint B7x induces resistance to anti-CTLA-4 therapy and that combination treatment of anti-B7x and anti-CTLA-4 leads to synergistic therapeutic efficacy and overcomes the resistance to anti-CTLA-4 therapy. Guided by our published clinical and basic research, and our strong preliminary data, we will pursue two specific aims: 1) Dissect the mechanisms underlying tumor-expressed B7x mediated resistance to anti-CTLA-4 therapy; and 2) Develop novel combination therapies of anti-B7x and anti-CTLA-4 to overcome the resistance. We have generated a number of novel tools for this project. The outcomes of this project will reveal new mechanisms underlying tumor-expressed B7x-mediated resistance to anti-CTLA-4 therapy and will develop into new immunotherapies overcoming the resistance.

肿瘤表达的免疫检查点 B7x 介导的耐药性抗CTLA-4治疗 CTLA-4 和 PD-1/PD-L1 的免疫检查点阻断已取得进展癌症患者的治疗。然而，最大的挑战之一是大多数癌症患者对这些治疗没有反应。基于我们的新结果，我们提出的修订研究的中心假设是肿瘤表达的免疫检查点 B7x 诱导抗 CTLA-4 耐药抗 B7x 和抗 CTLA-4 的联合治疗导致协同治疗功效并克服抗CTLA-4耐药性治疗。以我们发表的临床和基础研究为指导，以及我们强大的根据初步数据，我们将追求两个具体目标：1）剖析机制潜在的肿瘤表达的 B7x 介导的抗 CTLA-4 治疗耐药性； 2) 开发抗 B7x 和抗 CTLA-4 的新型联合疗法克服阻力。我们为此开发了许多新颖的工具项目。该项目的成果将揭示潜在的新机制肿瘤表达的 B7x 介导的抗 CTLA-4 治疗耐药性开发新的免疫疗法来克服耐药性。