Engineered TCR-T Cell Therapies Targeting Shared Tumor Associated Antigens

针对共享肿瘤相关抗原的工程 TCR-T 细胞疗法

• 批准号: 10324506
• 负责人: Matthew James Spindler
• 金额: $ 40万
• 依托单位: GIGAMUNE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324506
• 关键词: Address; Adoptive Cell Transfers; Alleles; Allogenic; Antigen Targeting; Antigens; Autologous; Avidity; Biological Assay; Biotechnology; CAR T cell therapy; CD19 gene; CTAG1 gene; Cancer Patient; Catalogs; Cells; Clinical; Clinical Research; Clinical Trials; Common Neoplasm; DNA sequencing; Development; Differentiation Antigens; Disease; Doctor of Philosophy; Engineering; Epitope spreading; Epitopes; FDA approved; Genes; Genetic Engineering; Genomics; HLA Antigens; Hematologic Neoplasms; Human; Immunogenomics; In Vitro; Libraries; Malignant Neoplasms; Microfluidics; Nature; Patients; Peptides; Phase; Population; Protocols documentation; Publishing; Refractory; Relapse; Small Business Innovation Research Grant; Solid Neoplasm; T cell response; T cell therapy; T-Lymphocyte; Technology; Testing; Testis; Tumor Antigens; Tumor Escape; Tumor-Infiltrating Lymphocytes; anti-cancer; anti-tumor immune response; antigen binding; cell killing; chimeric antigen receptor T cells; clinical efficacy; effective therapy; efficacy study; engineered T cells; high risk; improved; in vivo; interest; melanoma; novel; novel therapeutics; patient population; response; safety study; synovial sarcoma; targeted treatment; treatment response; tumor; tumor infiltrating lymphocyte therapy

PROJECT SUMMARY Project Title: Engineered TCR-T Cell Therapies Targeting Shared Tumor Associated Antigens Organization: GigaMune Inc. PI: Matthew J Spindler, Ph.D. Adoptive cell therapies (ACTs) including CAR-T, TCR-T, and TIL therapies have shown strong clinical responses for the treatment of cancer patients for hematological cancers and solid tumors. However, only anti-CD19 CAR- T cell therapies have been FDA approved and commercialized for the treatment of hematological cancers. Numerous TCR-T cell clinical trials are ongoing for the treatment of solid tumors, but these trials target only a handful of tumor associated antigens (TAAs) with the majority restricted to HLA-A0201. Thus, there is a need to develop novel anti-cancer TCR-T cell therapies for the treatment of a broader patient population. TAAs including cancer/testis and differentiation antigens are ideal TCR-T cell targets as they are shared across patients and solid tumor types and can induce T cell responses across numerous HLA alleles. Importantly, a recent clinical trial demonstrated that autologous anti-TAA T cells can provide strong anti-tumor efficacy in high- risk solid tumor patients. However, these autologous anti-TAA T cells require intensive ex vivo expansion and can result in variable anti-tumor reactivity. This suggests that TCR-T cell therapies targeting common TAAs would provide an effective treatment for solid tumor patients and improve manufacturing consistency and efficacy. The Specific Aim of this Phase I SBIR project is to develop a catalog of natural human TCRs that target shared tumor associated antigens for use in autologous or allogeneic TCR-T cells therapies. GigaMune's unique technology uses microfluidics, genomics, and mammalian display to generate millions-diverse, natively paired TCRab repertoire libraries. The TCRab libraries are immortal, enabling repeated experimentation with a panel of antigens. This will expedite discovery of rare anti-TAA TCRs. The project is led by Dr. Matthew J. Spindler, an expert in immunogenomics and inventor of the GigaMune technology and supported by serial entrepreneur and co-founder David Johnson (GigaGen). After completing this Phase I SBIR project, GigaMune will further develop promising TCRs as TCR-T cell therapies, through in vivo efficacy studies, in vitro safety studies, and manufacturing development.

项目总结 项目标题：针对共享肿瘤相关抗原的工程化TCR-T细胞疗法 组织：GigaMune Inc. 派：马修·J·斯宾德勒，博士。 过继细胞疗法(ACTs)包括CAR-T、TCR-T和TIL疗法，已显示出强烈的临床反应 用于治疗血液系统肿瘤和实体瘤的癌症患者。然而，只有抗CD19的汽车- T细胞疗法已获得FDA批准，并已商业化，用于治疗血液病癌症。 许多TCR-T细胞治疗实体瘤的临床试验正在进行中，但这些试验只针对一个 为数不多的肿瘤相关抗原(TAA)，大多数局限于人类白细胞抗原-A0201。因此，有必要 开发新的抗癌TCR-T细胞疗法，以治疗更广泛的患者群体。 包括癌症/睾丸和分化抗原在内的TAAs是理想的TCR-T细胞靶点，因为它们在 患者和实体肿瘤类型，并可以诱导T细胞反应跨越众多的HL A等位基因。重要的是，一个 最近的临床试验表明，自体抗TAA T细胞可在高危人群中提供强大的抗肿瘤效果。 实体肿瘤患者的风险。然而，这些自体抗TAA T细胞需要密集的体外扩增和 可导致不同的抗肿瘤反应性。这表明针对常见TAA的TCR-T细胞疗法 将为实体肿瘤患者提供有效的治疗并提高生产一致性和 功效。 这个第一阶段SBIR项目的具体目标是开发一个针对共享的天然人类TCR的目录 用于自体或同种异体TCR-T细胞治疗的肿瘤相关抗原。GigaMune的独特之处 技术使用微流体、基因组学和哺乳动物展示技术来产生数百万种不同的、天然配对的 TCRab曲目库。TCRab库是不朽的，可以在面板上重复实验 抗原性。这将加速发现罕见的抗TAA TCR。 该项目由免疫基因组学专家、GigaMune发明者Matthew J.Spindler博士领导 技术，并由连续创业者和联合创始人大卫·约翰逊(GigaGen)支持。完成后 这个第一阶段的SBIR项目，GigaMune将进一步开发有前景的TCR作为TCR-T细胞疗法，通过 体内疗效研究、体外安全性研究和制造开发。