SBIR INNOVATIVE CONCEPT AWARD - DETECTION, DIAGNOSIS, TREATMENT, PREVENTION AND RESEARCH OF PEDIATRIC CANCERS AND/OR RARE CANCERS

SBIR 创新概念奖 - 儿童癌症和/或罕见癌症的检测、诊断、治疗、预防和研究

• 批准号: 10586902
• 负责人: STEPHANIE HACHEY
• 金额: $ 35.5万
• 依托单位: IMMUNOTARGET THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-02 至 2023-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10586902
• 关键词: Autologous; Award; Cancer cell line; Cellular Immunity; Clinical; Detection; Diagnosis; Generations; Goals; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; In Vitro; Lead; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of esophagus; Mediating; Methods; Morbidity - disease rate; Mus; Patients; Population; Preparation; Prevention Research; Resistance; Small Business Innovation Research Grant; Specificity; T-Cell Immunologic Specificity; T-Lymphocyte; Testing; Therapeutic; Tissues; Tumor Escape; Tumor Immunity; Vaccines; Xenograft Model; cancer cell; early phase clinical trial; efficacy evaluation; efficacy testing; fighting; immunogenicity; improved; in vivo; in vivo evaluation; individual patient; innovation; mortality; mouse model; neoantigens; neoplastic cell; novel strategies; patient subsets; prevent; rare cancer; response; therapeutic vaccine; treatment strategy; tumor; vaccine efficacy

Immunotherapies harness the body’s own natural defenses to fight cancer and can lead to durable responses in some patients, but clinical benefit has remained limited. Therapeutic vaccines derived from whole tumor lysates are a promising treatment strategy that ares well tolerated and have shown promising results in early clinical trials, stimulating neoantigen-specific immune responses in a subset of patients. Yet the majority of patients are poorly responsive to vaccine treatment, underscoring the need to devise improved strategies for stimulating anti-tumor activity, and thereby preventing tumor escape. To induce robust cellular immunity against esophageal cancer, a rare but particularly aggressive malignancy that leads to significant morbidity and mortality in the US, our strategy is to optimally prime neoantigen-reactive T cells from individual patients with esophageal cancer. We propose an innovative priming method to induce neoantigens in tumor cells prior to lysate generation, thereby enhancing the immunogenicity of each vaccine preparation, and test efficacy and specificity in vitro. Finally, we will test in vivo efficacy of our therapeutic preparation using a mouse model of esophageal cancer. Our goal is to advance novel approaches to effectively mobilize anti-tumor immunity, improve therapeutic vaccine efficacy and overcome immunotherapeutic resistance in esophageal cancer.

免疫疗法利用人体自身的自然防御系统来抗击癌症，并可带来持久的 在一些患者中有反应，但临床益处仍然有限。治疗性疫苗源于 全肿瘤裂解物是一种有希望的治疗策略，耐受性良好，并已显示出良好的前景。 结果在早期临床试验中，在部分患者中刺激了新抗原特异性免疫反应。还没有 大多数患者对疫苗治疗反应不佳，强调了设计 改进了激发抗肿瘤活性的策略，从而防止肿瘤逃逸。诱使 针对食道癌的强大细胞免疫功能，食道癌是一种罕见但特别侵袭性的恶性肿瘤，它导致 对于美国的显著发病率和死亡率，我们的策略是最佳地启动新抗原反应性T细胞 来自个别食道癌患者。我们提出了一种创新的启动方法来诱导 在裂解物生成之前的肿瘤细胞中的新抗原，从而增强每种疫苗的免疫原性 制备，并进行体外药效和特异性试验。最后，我们将在体内测试我们的治疗效果 用小鼠食道癌模型制备。我们的目标是推进新的方法来 有效调动抗肿瘤免疫，提高治疗性疫苗效力，克服 食道癌的免疫治疗耐药。