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.