Development of a Therapeutic SAPNANO-ESO Vaccine for Prostate Cancer

开发治疗前列腺癌的 SAPNANO-ESO 疫苗

• 批准号: 10662536
• 负责人: Yicheng Wang
• 金额: $ 100万
• 依托单位: IMMUNOVA THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10662536
• 关键词: Acceleration; Address; Antibodies; Antigens; Antitumor Response; Biodistribution; CD8-Positive T-Lymphocytes; CTAG1 gene; Cancer Etiology; Cancer Patient; Cancer Vaccines; Cells; Cessation of life; Clinical Research; Data; Dendritic Cells; Development; Dose; Drug Kinetics; Epitopes; Future; HLA-A2 Antigen; HLA-DP4; Immune; Immunity; Immunosuppression; Immunotherapy; In Vitro; Intravenous; Investigational Drugs; Investigational New Drug Application; Ligands; Maintenance; Malignant Neoplasms; Malignant neoplasm of prostate; Medical; Metastatic Prostate Cancer; Mission; Modeling; Mus; Myeloid-derived suppressor cells; Normal tissue morphology; Outcome; PD-1 blockade; PD-1/PD-L1; Peptides; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase I Clinical Trials; Poly I-C; Positioning Attribute; Prostate Cancer Vaccine; Provenge; Regulatory T-Lymphocyte; Route; Safety; Signal Transduction; Site; Small Business Innovation Research Grant; Solid; T cell response; T-Lymphocyte; Technology; Temperature; Testing; Testis; Therapeutic; Toll-like receptors; Toxic effect; Transgenic Organisms; Tumor Immunity; Tumor-associated macrophages; United States; Vaccines; cancer immunotherapy; cancer type; cancer/testis antigen; checkpoint therapy; immune checkpoint blockade; immunogenic; innovation; innovative technologies; men; mouse model; nanoparticle; novel; novel strategies; novel vaccines; pharmacologic; preclinical study; product development; prostate cancer cell; self assembly; stability testing; therapeutic development; therapeutic vaccine; tumor; vaccine immunotherapy

Project Summary/Abstract Prostate cancer is a leading cause of cancer-related deaths of men in the United States and worldwide. Immunotherapy is a promising approach, but has not proven successful yet in prostate cancer. Hence, metastatic prostate cancer remains an important unmet medical need. To address this unmet medical need, we recently developed a novel vaccine technology, called self-assembled peptide nanoparticles (SAPNANO) vaccines. Immunova Therapeutics is a startup company with the mission to further develop the SAPNANO-ESO vaccine product (or IMT-001) for the treatment of NY-ESO-1 positive cancer, including prostate cancer. This IMT-001 product induces robust antitumor responses, resulting in marked inhibition or even elimination of prostate tumor cells in a mouse model. The key features of the ITM-001 product include intravenous delivery without dendritic cells and the ability to induce robust and therapeutic antitumor immunity, which is distinguished from other vaccine technologies that fail to induce therapeutic immunity. Increasing evidence suggests that the maintenance and expansion of vaccine-induced T cells may be inhibited by multiple suppressive mechanisms at tumor sites, including the intrinsic co-inhibitory PD-1/PD-L1 signaling, Treg cells, tumor-associated macrophages and MDSCs, thus posing major obstacles for effective vaccine and immunotherapy. It is likely that IMT-001 vaccine- induced antitumor immunity could be further enhanced by anti-PD-1 blockade. In this application, we will determine the stability of IMT-001 vaccine product in vitro and optimal doses and delivery routes for therapeutic antitumor immunity in mouse tumor models (Aim 1), conduct investigational new drug (IND)-enabling studies of the biodistribution and pharmacological toxicities (Aim 2), and finally test whether IMT-001 vaccine-induced therapeutic antitumor immunity can be further enhanced by of PD-1 blockade therapy (Aim 3). Upon completion of the proposed studies, we should have completed the IND-enabling studies and are well positioned to submit an IND for a phase I clinical trial. This SBIR support is critically important for Immunova Therapeutics to accelerate the development of new cancer vaccine product/drug for the treatment of metastatic prostate cancer, as well as other NY-ESO-1 positive cancers.

项目摘要/摘要 前列腺癌是美国和全球男性与癌症相关死亡的主要原因。 免疫疗法是一种有前途的方法，但尚未证明在前列腺癌中成功。因此，转移 前列腺癌仍然是重要的未满足医疗需求。为了满足这种未满足的医疗需求，我们最近 开发了一种新型的疫苗技术，称为自组装肽纳米颗粒（Sapnano）疫苗。 Immunova Therapeutics是一家创业公司，其使命是进一步开发Sapnano-Eso疫苗 用于治疗NY-ESO-1阳性癌症（包括前列腺癌）的产品（或IMT-001）。此IMT-001 产品诱导强大的抗肿瘤反应，从而导致明显的抑制甚至消除前列腺肿瘤 小鼠模型中的细胞。 ITM-001产品的关键特征包括静脉输送而无需树突状 细胞和诱导鲁棒和治疗性抗肿瘤免疫的能力，这与其他区别 无法诱导治疗免疫的疫苗技术。越来越多的证据表明维护 疫苗诱导的T细胞的扩展可能会受到肿瘤部位的多种抑制机制的抑制， 包括内在的共抑制性PD-1/PD-L1信号传导，Treg细胞，肿瘤相关的巨噬细胞和 MDSC，从而构成了有效疫苗和免疫疗法的主要障碍。 IMT-001疫苗可能很可能 抗PD-1阻断可以进一步增强诱导的抗肿瘤免疫力。在此应用程序中，我们将 确定IMT-001疫苗产品在体外和最佳剂量以及治疗途径的稳定性 小鼠肿瘤模型中的抗肿瘤免疫力（AIM 1），进行研究新药（IND） - 增强对 生物分布和药理毒性（AIM 2），最后测试IMT-001疫苗诱导 可以通过PD-1阻滞疗法进一步增强治疗性抗肿瘤免疫力（AIM 3）。完成后 在拟议的研究中，我们应该已经完成​​了成熟的研究，并且有能力提交 I期临床试验的IND。这种SBIR支持对于免疫疗法至关重要 加速新的癌症疫苗产品/药物以治疗转移性前列腺癌， 以及其他NY-ESO-1阳性癌症。