STING Activators as Therapy for Cancer

STING 激活剂治疗癌症

基本信息

批准号：
10480641
负责人：
JEONGHYUN AHN
金额：
$ 99.32万
依托单位：
STINGINN, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-17 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480641
关键词：
Acute Myelocytic Leukemia Adjuvant Adult Adult T-Cell Leukemia/Lymphoma Agonist Antigen-Presenting Cells Antitumor Response Apoptotic Autoimmunity Autologous Autologous Tumor Cell Bacteria Barbering Biological Biotechnology Blood CAR T cell therapy CD8B1 gene Cell Death Cell Lineage Cell Nucleus Cell division Cells Cellular immunotherapy Clinic Clinical Clinical Data Clinical Trials Collaborations Communicable Diseases Cross Presentation Cyclic GMP Cytosol Cytotoxic T-Lymphocytes DNA DNA Damage Data Dendritic Cells Deoxyribonucleases Development Dinucleoside Phosphates Disease Embryo Event Exodeoxyribonuclease III FDA approved Future Generations Hematologic Neoplasms Host Defense Human Human T-lymphotropic virus 1 Immune Immune signaling Immune system Immunologics Immunooncology Immunotherapeutic agent In Vitro Infection Inflammation Interferon Type I Invaded Laboratories Lead Length Letters Leukemic Cell Lymphoblastic Leukemia Lymphoid Cell Malignant - descriptor Malignant Neoplasms Modeling Mus Myeloid Cells Myeloid Leukemia Normal Cell Nucleic Acids Nucleotides Participant Patients Periodicity Phagocytes Phagocytosis Phase I Clinical Trials Play Process Production Property Proteins Refractory Relapse Research Research Personnel Resistance Role STING agonists Safety Signal Pathway Signal Transduction Stimulator of Interferon Genes T-Cell Leukemia T-Lymphocyte Techniques Technology Testing Therapeutic Therapeutic Trials Three Prime Repair Exonuclease 1 Toxic effect Tumor Antigens Tumor Burden Tumor Immunity Universities Work animal data anti-cancer anti-tumor immune response antigen-specific T cells base cancer cell cancer therapy conventional therapy cytokine defense response ds-DNA fighting immunogenic in vivo inhibitor leukemia macrophage microbial mouse model neoplastic cell novel novel strategies personalized approach phase I trial pilot trial pre-clinical prevent sensor tumor ultraviolet irradiation

项目摘要

PROJECT SUMMARY The Immuno-oncology (IO) arena affords a new and exciting approach to stimulate the body’s own immune system to fight cancer. The generation of anti-cancer T cells is predominantly triggered by phagocytosed cancer cells stimulating innate immune signaling pathways in professional antigen presenting cells (APC’s). This signaling process is largely governed by STING (stimulator of interferon genes), a cellular protein discovered by the laboratory of Dr. Glen N. Barber that plays an essential role in host defense against infectious disease and cancer. Activation of STING triggers cytokine production and facilitates tumor antigen cross-presentation. Indeed, considerable effort is now underway in the biotech arena to discover techniques to augment STING activity with the objective of invigorating the generation of anti-tumor cytotoxic T cells. Along with check-point inhibitors and CAR-T cell therapy, the plausible utilization of STING agonists affords a new, complementary immunotherapeutic strategy to treat malignant disease. Here, STINGINN, LLC (“STINGINN”), in collaboration with the University of Miami, proposes to perform an FDA approved investigator sponsored small Phase I clinical trial for patients suffering from highly aggressive leukemias, specifically relapsed/refractory acute myeloid leukemia (AML) and adult lymphocytic leukemia (ALL) focusing on HTLV-1 associated adult T cell lymphocytic leukemia (ATLL). Our strategy involves reinfusing autologous tumor cells loaded with STING-dependent adjuvants (STAVs) into patients to stimulate APCs in vivo and thus anti-tumor CTL’s. Our pre-clinical data indicates that STAV loaded cells are highly immunogenic, potent activators of APC’s. We have already submitted an IND FDA application based on this work and have assembled an appropriate team to carry out the proposed trial. Our proposal is also applicable to a variety of cancers, not just leukemia, providing the opportunity to initiate a number of alternate cancer therapeutic trials in the future.

项目概要免疫肿瘤学 (IO) 领域提供了一种令人兴奋的新方法来刺激人体自身的免疫抗癌 T 细胞的产生主要是由吞噬癌症引发的。细胞刺激专业抗原呈递细胞（APC）中的先天免疫信号通路。信号传导过程主要受 STING（干扰素基因刺激剂）控制，STING 是一种细胞蛋白，由 Glen N. Barber 博士的实验室在宿主防御传染病和 STING 的激活会触发细胞因子的产生并促进肿瘤抗原的交叉呈递。事实上，生物技术领域目前正在付出巨大努力来发现增强 STING 的技术活性的目的是与检查点一起促进抗肿瘤细胞毒性 T 细胞的产生。抑制剂和 CAR-T 细胞疗法，STING 激动剂的合理使用提供了一种新的、互补的治疗恶性疾病的免疫治疗策略。在这里，STINGINN, LLC（“STINGINN”）与迈阿密大学合作，建议进行 FDA 批准的研究者赞助了针对高度侵袭性患者的小型 I 期临床试验白血病，特别是复发/难治性急性髓系白血病 (AML) 和成人淋巴细胞白血病 (ALL) HTLV-1 相关的成人 T 细胞淋巴细胞白血病 (ATLL) 我们的策略包括回输。将负载有 STING 依赖性佐剂 (STAV) 的自体肿瘤细胞注入患者体内以刺激体内 APC 因此，我们的临床前数据表明，负载 STAV 的细胞具有高度免疫原性、有效。我们已经根据这项工作向 FDA 提交了 IND 申请并已组装完毕。一个合适的团队来进行拟议的试验，我们的建议也适用于多种癌症，而不是。只是白血病，为未来启动一些替代癌症治疗试验提供了机会。