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

项目摘要/摘要 预计今年全世界将有880万人死于癌症。在美国，它是导致死亡的主要原因， 患病率每年持续增长。常规治疗方案往往疗效有限 并且经常伴随有害的副作用。较新的基于抗体和基于细胞的疗法 分别显示出对实体肿瘤和血液学癌症子集特别有希望。重要的是， 虽然这些新的治疗方法已经显示出了希望，但它们通常只对一小部分人有效。 患者或伴有严重的副作用。实体瘤癌症患者往往有最贫穷的 成果和成果。这可能是由于癌症对患者免疫系统的强烈抑制 细胞信号该提案旨在克服肿瘤免疫抑制的关键机制 微环境，以释放新类别癌症治疗的全部潜力。重要的是， 利用替代信号通路，这显示出增强免疫系统功能的希望。 通过这一I期SBIR，Javelin Oncology旨在提供临床前概念验证， 治疗可以增强当前一代细胞疗法的功能，以释放它们的潜力， 治疗实体癌这些实验将推动选择一种领先的治疗方法，并证明IND- 使得能够进行制备这些用于递送给患者的新型治疗剂所需的临床前工作。

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.