Development of a Therapeutic SAPNANO-ESO Vaccine for Prostate Cancer

项目总结/摘要 前列腺癌是美国和世界范围内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，但在前列腺癌中尚未证明成功。因此是转移性的 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 开发了一种新的疫苗技术，称为自组装肽纳米颗粒（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 本发明涉及用于治疗NY-ESO-1阳性癌症（包括前列腺癌）的药物组合物（或IMT-001）。此IMT-001 本品可诱导强大的抗肿瘤反应，从而显著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静脉内给药， 细胞和诱导强大的和治疗性的抗肿瘤免疫的能力，这是区别于其他 不能诱导治疗性免疫的疫苗技术。越来越多的证据表明， 并且疫苗诱导的T细胞的扩增可被肿瘤部位的多种抑制机制抑制， 包括内源性共抑制PD-1/PD-L1信号传导、Treg细胞、肿瘤相关巨噬细胞和 MDSC，从而对有效的疫苗和免疫疗法构成主要障碍。IMT-001疫苗可能- 诱导的抗肿瘤免疫可通过抗PD-1阻断进一步增强。在这个应用程序中，我们将 确定IMT-001疫苗产品在体外的稳定性以及治疗的最佳剂量和递送途径 在小鼠肿瘤模型中的抗肿瘤免疫（目标1），进行研究性新药（IND）使能研究， 生物学分布和药理学毒性（目的2），并最终测试IMT-001疫苗是否诱导 治疗性抗肿瘤免疫可通过PD-1阻断疗法进一步增强（目的3）。完成后 在建议的研究中，我们应该已经完成了IND的可行性研究，并有能力提交 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.