Development of Therapeutic Cancer Vaccine

治疗性癌症疫苗的开发

• 批准号: 10324856
• 负责人: Shu-Hsia Chen
• 金额: $ 39.57万
• 依托单位: IMMUNOQ 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: 2022-06-06 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324856
• 关键词: Adjuvant; Antibodies; Antibody-drug conjugates; Antigen Presentation Pathway; Antigen-Presenting Cells; Antigens; Beds; Biological Assay; CD8-Positive T-Lymphocytes; Cancer Patient; Cancer Vaccine Related Development; Cancer Vaccines; Cell Differentiation process; Cells; Clinic; Clinical Trials; Cyclic GMP; Dendritic Cells; Dendritic cell activation; Development; Disease; Distant; ERBB2 gene; Essential Genes; Foundations; Goals; Head and Neck Cancer; Human; Immune; Immunotherapy; Implant; Incidence; Innate Immune Response; Interferon Type I; Interferon-alpha; Investigational Drugs; Knockout Mice; Ligands; Maintenance; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Medical; Modeling; Mus; Neoplasm Metastasis; Organ; Particulate; Patients; Peptides; Pharmaceutical Preparations; Phase; Play; Preparation; Primary Neoplasm; Property; Proteins; Quality Control; Quality of life; Receptor Protein-Tyrosine Kinases; Research; Resistance development; Role; STING agonists; Silicon; Small Business Technology Transfer Research; T-Lymphocyte; TLR9 gene; TNF gene; Testing; Text; Therapeutic; Therapeutic antibodies; Translating; Treatment Efficacy; Tumor Immunity; Tumor-infiltrating immune cells; United States; Vaccination; Vaccines; Wild Type Mouse; anti-PD-1; anti-PD-L1 antibodies; anti-tumor immune response; anticancer activity; base; cancer cell; cancer therapy; cancer type; combat; cytokine; drug candidate; effective therapy; fight against; fighting; human disease; humanized mouse; immune checkpoint blockade; immunogenic; improved; malignant breast neoplasm; malignant stomach neoplasm; nanometer; nanopore; novel; overexpression; particle; public health relevance; quality assurance; side effect; small molecule; small molecule inhibitor; success; targeted treatment; therapeutic development; therapeutic vaccine; therapy resistant; tumor; tumor-immune system interactions; uptake; vaccine evaluation

ABSTRACT (no more than 30 lines of text) HER2-positive breast cancer accounts for 20-30% of all breast cancer incidences. Although there are small molecule inhibitors targeting the HER2 receptor tyrosine kinase and therapeutic antibodies specific for the HER2 protein, tens of thousands of patients still die of late-stage HER2-positive breast cancer every year. In the pursuit for novel and effective treatments, we recently developed a therapeutic cancer vaccine for HER2-positive breast cancer. This vaccine is composed of HER2-specific antigen peptides and soluble adjuvants that are loaded into the nanopores of a porous particulate adjuvant. The final therapeutic vaccine product has a number of unique properties that makes it highly effective including, but not limited to, maintenance of vaccine particle integrity for coordinated functions, preferential uptake and transport by dendritic cells, synergistical stimulation of dendritic cells by promoting secretion of type I interferons and TNF-a, and long-term vaccine activity as a result of sustained release of antigen peptides and soluble adjuvants. Our preliminary studies with murine HER2-positive tumors have revealed that vaccine treatment can stimulate proliferation of HER2 antigen-specific CD8+ T cells and infiltration of T cells into the tumor bed, leading to inhibition of both primary and metastatic tumors. In addition, vaccination does not cause detectable adverse side effects, making it an excellent candidate drug. In this STTR phase I project, we propose studies to further understand the mechanism of action from the therapeutic cancer vaccine and to establish human disease relevance. In the Aim 1 study, we will test the hypothesis that conventional dendritic cells are essential for anti-tumor activity from the vaccine. In the Aim 2 study, we will test the hypothesis that anti-tumor activities observed in murine tumor models can be replicated in humanized mice bearing human HER2-positive cancers. During the course of the study, we will also establish a set of assays for quality control and quality assurance. Upon completion of these studies, we will submit a phase II proposal to support investigational new drug (IND)-enabling studies in preparation for human clinical trials.

摘要（不超过30行文字） HER2 阳性乳腺癌占所有乳腺癌发病率的 20-30%。虽然也有小 针对 HER2 受体酪氨酸激酶的分子抑制剂和针对 HER2 受体酪氨酸激酶的特异性治疗抗体 HER2蛋白，每年仍有数以万计的患者死于晚期HER2阳性乳腺癌。 为了寻求新颖有效的治疗方法，我们最近开发了一种治疗性癌症疫苗 HER2 阳性乳腺癌。该疫苗由HER2特异性抗原肽和可溶性抗原肽组成。 负载到多孔颗粒佐剂的纳米孔中的佐剂。最终的治疗性疫苗 产品具有许多独特的特性，使其非常有效，包括但不限于： 维持疫苗颗粒的完整性以协调功能、优先摄取和运输 树突状细胞，通过促进 I 型干扰素的分泌来协同刺激树突状细胞 TNF-a 和由于抗原肽和可溶性物质持续释放而产生的长期疫苗活性 佐剂。我们对小鼠 HER2 阳性肿瘤的初步研究表明，疫苗治疗 可以刺激 HER2 抗原特异性 CD8+ T 细胞增殖和 T 细胞浸润到肿瘤中 床，从而抑制原发性和转移性肿瘤。此外，接种疫苗不会导致 可检测到的不良副作用，使其成为极好的候选药物。在这个 STTR 第一阶段项目中，我们 提出研究以进一步了解治疗性癌症疫苗的作用机制并 建立人类疾病相关性。在目标 1 研究中，我们将检验以下假设：传统 树突状细胞对于疫苗的抗肿瘤活性至关重要。在 Aim 2 研究中，我们将测试 假设在小鼠肿瘤模型中观察到的抗肿瘤活性可以在人源化小鼠中复制 携带人类 HER2 阳性癌症。在研究过程中，我们还将建立一套分析方法 用于质量控制和质量保证。完成这些研究后，我们将提交 II 期研究 提议支持研究性新药（IND）研究，为人体临床试验做准备。