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

嵌合开关受体增强 CAR T 细胞治疗实体瘤的能力

• 批准号: 10483928
• 负责人: Anthony Cooper
• 金额: $ 32.89万
• 依托单位: JAVELIN ONCOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483928
• 关键词: American; Animals; Antibodies; Antigen Targeting; Antigens; Binding; CAR T cell therapy; Cancer Patient; Cause of Death; Cell Therapy; Cell physiology; Cells; Chimera organism; Coculture Techniques; Combined Modality Therapy; Coupling; Cultured Cells; Disease; Dominant-Negative Mutation; Effectiveness; Engineering; Event; Family; Flow Cytometry; Future; Generations; Goals; Hematologic Neoplasms; Immune; Immune system; Immunosuppression; In Vitro; Infiltration; Infusion procedures; Interleukin-2; Jurkat Cells; Lead; Malignant Neoplasms; Measures; Mediating; Modeling; Mus; Nature; Oncology; Outcome; Patients; Phase; Positioning Attribute; Prevalence; Production; Prognosis; Receptor Activation; Receptor Cell; Receptor Signaling; Role; Signal Pathway; Signal Transduction; Small Business Innovation Research Grant; Solid; Solid Neoplasm; T-Cell Activation; T-Lymphocyte; Technology; Testing; Therapeutic; Toll-like receptors; Tumor Antigens; Tumor Cell Line; Variant; Work; base; bioluminescence imaging; cancer cell; cell killing; checkpoint inhibition; chimeric antigen receptor; chimeric antigen receptor T cells; conventional therapy; cytokine; design; exhaustion; experimental study; extracellular; immune checkpoint; immune system function; in vivo; neoplastic cell; novel; novel therapeutics; patient subsets; pre-clinical; programmed cell death ligand 1; programmed cell death protein 1; receptor; receptor expression; response; side effect; tumor; tumor microenvironment; tumor xenograft

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.

项目摘要/总结 癌症预计今年将夺走全球 880 万人的生命。在美国，它是导致死亡的主要原因 患病率每年持续增长。传统治疗方案的疗效往往有限 并且常常伴随着有害的副作用。较新的基于抗体和细胞的疗法已经 分别对实体瘤和血液癌的子集显示出特别的希望。重要的是， 虽然这些新疗法已显示出希望，但它们通常仅在一小部分范围内有效。 患者或伴有严重副作用。实体瘤癌症患者往往生活最贫困 预测和结果。这可能是由于癌症驱动的患者免疫系统受到强烈抑制 细胞信号传导。该提案旨在克服肿瘤免疫抑制的关键机制 微环境释放新型癌症治疗的全部潜力。重要的是，技术 利用替代信号通路，有望增强免疫系统功能。 通过这一 I 期 SBIR，Javelin Oncology 打算提供临床前概念验证，即一种新型药物 治疗可以增强当前一代细胞疗法的功能，以释放其潜力 治疗实体癌症。这些实验将推动主要治疗药物的选择并证明 IND- 开展准备这些新疗法以交付给患者所需的临床前工作。