Development of a Therapeutic SAPNANO-ESO Vaccine for Prostate Cancer

项目概要/摘要 前列腺癌是美国和全世界男性癌症相关死亡的主要原因。 免疫疗法是一种很有前途的方法，但尚未证明在前列腺癌中成功。因此，转移性 前列腺癌仍然是一个重要的未满足的医疗需求。为了解决这一未满足的医疗需求，我们最近 开发了一种新型疫苗技术，称为自组装肽纳米粒子（SAPNANO）疫苗。 Immunova Therapeutics 是一家初创公司，其使命是进一步开发 SAPNANO-ESO 疫苗 产品（或 IMT-001）用于治疗 NY-ESO-1 阳性癌症，包括前列腺癌。这个IMT-001 产品诱导强大的抗肿瘤反应，从而显着抑制甚至消除前列腺肿瘤 小鼠模型中的细胞。 ITM-001产品的主要特点包括无树突静脉注射 细胞以及诱导强大的治疗性抗肿瘤免疫的能力，这与其他药物不同 无法诱导治疗性免疫的疫苗技术。越来越多的证据表明，维护 疫苗诱导的 T 细胞的扩增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、肿瘤相关巨噬细胞和 MDSCs，因此对有效的疫苗和免疫治疗构成了主要障碍。 IMT-001疫苗很可能- 抗PD-1阻断可以进一步增强诱导的抗肿瘤免疫。在这个应用程序中，我们将 确定 IMT-001 疫苗产品的体外稳定性以及治疗的最佳剂量和递送途径 小鼠肿瘤模型中的抗肿瘤免疫（目标 1），开展研究性新药 (IND) 启用研究 生物分布和药理毒性（目标2），最后测试IMT-001疫苗是否诱导 PD-1阻断疗法可以进一步增强治疗性抗肿瘤免疫（目标3）。完成后 在拟议的研究中，我们应该已经完成了 IND 授权研究，并准备好提交 I 期临床试验的 IND。这种 SBIR 支持对于 Immunova Therapeutics 至关重要 加速开发用于治疗转移性前列腺癌的新癌症疫苗产品/药物， 以及其他 NY-ESO-1 阳性癌症。

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.