STING Activators as Therapy for Cancer

项目总结 免疫肿瘤学(IO)领域提供了一种新的令人兴奋的方法来刺激人体自身的免疫力 抗击癌症的系统。抗癌T细胞的产生主要是由吞噬细胞癌触发的 刺激专业抗原提呈细胞(APC‘s)的先天免疫信号通路的细胞。这 信号传递过程在很大程度上由STIN(干扰素基因刺激物)控制，这是一种由 格伦·N·巴伯博士的实验室，在宿主防御传染病和 癌症。STING的激活会触发细胞因子的产生，并促进肿瘤抗原的交叉提呈。 事实上，目前生物技术领域正在进行相当大的努力，以发现增强刺痛的技术。 具有刺激产生抗肿瘤细胞毒性T细胞的活性。以及检查点 抑制剂和CAR-T细胞疗法，对STING激动剂的合理利用提供了一种新的、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，提议进行FDA 批准的研究人员赞助的小型I期临床试验，适用于患有高度侵袭性疾病的患者 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) 关注与HTLV-1相关的成人T淋巴细胞白血病(ATLL)。我们的策略包括重新注入 携带刺激性佐剂的自体肿瘤细胞体内刺激APC的实验研究 从而抗肿瘤CTL。我们的临床前数据表明，STIV负载的细胞具有高度的免疫原性， APC的激活剂。我们已经基于这项工作提交了IND FDA申请，并组装了 一个适当的团队来执行拟议的试验。我们的建议也适用于多种癌症，而不是 仅仅是白血病，提供了在未来启动一些替代癌症治疗试验的机会。

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.