Development of a Therapeutic SAPNANO-ESO Vaccine for Prostate Cancer

项目摘要/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，但尚未被证明对前列腺癌有效。因此，转移 前列腺癌仍然是一个重要的未得到满足的医疗需求。为了解决这一未得到满足的医疗需求，我们最近 开发了一种新的疫苗技术，称为自组装肽纳米粒(SAPNANO)疫苗。 免疫治疗公司是一家初创公司，其使命是进一步开发SAPNANO-ESO疫苗 该产品(或IMT-001)用于治疗NY-ESO-1阳性癌症，包括前列腺癌。这款IMT-001 产品可诱导强烈的抗肿瘤反应，显著抑制甚至消除前列腺癌。 小鼠模型中的细胞。ITM-001产品的主要特点包括静脉注射无树突状细胞 细胞和诱导强大的、治疗性的抗肿瘤免疫的能力，这与其他 未能诱导治疗性免疫的疫苗技术。越来越多的证据表明， 疫苗诱导的T细胞的扩增可能受到肿瘤部位多种抑制机制的抑制， 包括内源性共抑制PD-1/PD-L1信号、Treg细胞、肿瘤相关巨噬细胞和 因此，对有效的疫苗和免疫疗法构成了重大障碍。很可能IMT-001疫苗- 阻断PD-1可进一步增强诱导的抗肿瘤免疫。在此应用程序中，我们将 IMT-001疫苗制品体外稳定性及最佳给药剂量和给药途径的确定 小鼠肿瘤模型中的抗肿瘤免疫(目标1)，进行新药(IND)使能研究 生物分布和药理毒性(目标2)，最后检测IMT-001疫苗是否诱导 PD-1阻断治疗可进一步增强治疗性抗肿瘤免疫(目标3)。完工后 在建议的研究中，我们应该已经完成了支持IND的研究，并处于有利地位，可以提交 一期临床试验的IND。这种SBIR支持对于免疫治疗公司来说至关重要 加快开发治疗转移性前列腺癌的癌症疫苗新产品/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.