Exploring Coronavirus-specific T Cell Responses for Immunomonitoring and Adoptive Immunotherapy of COVID-19 in Cancer Patients

The outbreak of novel coronavirus (SARS-CoV2) causing Coronavirus Disease 2019 (COVID19) has disproportionally affected vulnerable populations including elderly and patients with co-morbidities, including history of cancer and hematopoietic stem cell transplant (SCT) and other defects of immunity. Here we will study the ex vivo T cell responses to SARS CoV2 and related hCoVs 229E and OC43 as a measure of immunocompetence (future diagnostics) and as a possible adoptive transfer strategy (prophylaxis) in high risk patients. Long-lived coronavirus-specific T (CoVST) cell memory responses exist in survivors of SARS and MERS infections and recently described in COVID19 survivors and some unexposed individuals, likely because of the previous exposures to common human CoVs (hCoVs, i.e. 229E and OC43). Based on our preliminary data we hypothesize that cross-reactivity between SARS-CoV2 antigens and their counterparts from common hCoVs exists, potentially contributing to broader anti-CoV protection in some individuals. Responses in cancer patients and SCT recipients (exposed and unexposed to SARS-CoV2) will be characterized in comparison to healthy controls (exposed and unexposed) as a basis for the development of the future research/diagnostic tool evaluating T cell immunity against SARS-CoV2 in correlation with serological testing. Ex vivo generated virus specific T (VST) cells have emerged as a powerful, safe, and cost-effective strategy allowing for rapid induction or restoration of anti-viral immunity. We hypothesize that it is feasible to efficiently induce and expand T cells concurrently recognizing immunodominant antigens of SARSCoV2 and common hCoVs using our standard clinically compatible methodology as a strategy for developing cell-based immunoprophylaxis. Ultimately, we will scale up the manufacturing process of potent cross-reactive allogeneic or autologous CoVSTs and rapidly obtain IND approval providing the basis for the future Phase I safety and feasibility study of adoptive transfer immune prophylaxis for SCT recipients and other vulnerable subjects with cancer as the rapidly accessible ex vivo alternative to vaccination.