Chimeric Switch Receptors to Potentiate CAR T Cell Therapy for Solid Tumor Cancers

项目摘要/摘要 预计今年全球癌症将夺走880万人的生命。在美国，它是主要的死亡原因， 这一流行率每年都在持续增长。传统的治疗方案往往在疗效上受到限制。 而且经常伴随着有害的副作用。新的基于抗体和基于细胞的疗法已经 分别对实体瘤和血液性癌症的子集显示出特别的前景。重要的是 虽然这些新疗法显示出了希望，但它们通常只在一小部分脑部疾病中有效。 患者或伴有严重副作用。实体肿瘤患者往往是最贫穷的 预测和结果。这可能是由于癌症对患者免疫系统的强烈抑制。 细胞信号。这项建议旨在克服肿瘤中免疫抑制的关键机制。 微环境，以释放新的癌症治疗类别的全部潜力。重要的是，这项技术 利用替代的信号通路，显示出增强免疫系统功能的希望。 通过这项第一阶段SBIR，标枪肿瘤学打算提供临床前概念证明，即一种新的 治疗可以增强当前一代细胞疗法的功能，以释放其潜在的 治疗实体癌症。这些实验将推动铅治疗药物的选择，并证明IND- 使准备这些新疗法交付给患者所需的临床前工作成为可能。

Project Abstract/Summary Cancer is expected to claim 8.8 million lives worldwide this year. In the US, it is the leading cause of death with a prevalence that continues to grow each year. Conventional treatment options tend to be limited in efficacy and are often accompanied by deleterious side effects. Newer antibody-based and cell-based therapies have shown particular promise for a subset of solid tumor and hematological cancers, respectively. Importantly, while these new therapies have shown promise, they are often only effective in a small cross-section of patients or are accompanied by severe side effects. Solid tumor cancer patients tend to have the poorest prognoses and outcomes. This is likely due strong suppression of patients’ immune systems driven by cancer cell signaling. This proposal aims to overcome key mechanisms of immune suppression in the tumor microenvironment to unlock the full potential of new classes of cancer therapeutics. Importantly, the technology leverages alternative signaling pathways which show promise for enhancing immune system function. With this Phase I SBIR, Javelin Oncology intends to provide preclinical proof-of-concept that a novel therapeutic can enhance the function of the current generation of cellular therapies to unlock their potential for treating solid cancers. These experiments will drive the selection of a lead therapeutic and justify the IND- enabling preclinical work required to prepare these novel therapeutics for delivery to patients.