STING Activators as Therapy for Cancer

项目摘要 免疫肿瘤学（IO）竞技场提供了一种新的和令人兴奋的方法来刺激人体自身的免疫 系统对抗癌症。抗癌T细胞的产生主要由吞噬的癌症触发 在专职抗原呈递细胞（APC）中刺激先天免疫信号传导途径的细胞。这 信号传导过程主要由STING（干扰素基因刺激因子）控制，STING是一种由 Glen N博士的实验室。理发师，发挥重要作用，在宿主防御传染病， 癌STING的激活触发细胞因子产生并促进肿瘤抗原交叉呈递。 事实上，在生物技术竞技场中正在进行相当大的努力，以发现增强STING的技术 活性，目的是促进抗肿瘤细胞毒性T细胞的产生。沿着检查点 尽管STING抑制剂和CAR-T细胞疗法的应用是可行的，但STING激动剂的合理利用提供了一种新的互补疗法。 免疫策略治疗恶性疾病。 在这里，STINGINN，LLC（“STINGINN”）与迈阿密大学合作，建议执行FDA 批准的研究者申办的小型I期临床试验，用于患有高度侵袭性 白血病，特别是复发性/难治性急性髓性白血病（AML）和成人淋巴细胞白血病（ALL） 专注于HTLV-1相关的成人T细胞淋巴细胞白血病（ATLL）。我们的策略是 将装载有STING依赖性佐剂（STAV）的自体肿瘤细胞植入患者体内以在体内刺激APC 从而产生抗肿瘤CTL。我们的临床前数据表明，STAV负载的细胞是高度免疫原性的，有效的， APC的激活剂。我们已经基于这项工作提交了IND FDA申请， 一个合适的团队来进行拟议的试验。我们的建议也适用于各种癌症， 只是白血病，提供了机会，在未来启动一些替代癌症治疗试验。

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.