Deep Phenotyping Reveals Evolution in T cell Phenotype after Hexaviral-specific T cell Infusion Post Hematopoietic Stem Cell Transplant

Viral infections are common following hematopoietic stem cell transplant (HCT) and multivirus-specific T cell therapies have been utilized to treat or prevent several viral infections and reactivation. In this study, we evaluated a novel donor-derived hexaviral specific T cell (hVST) product targeting cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr Virus (EBV), human polyomavirus (BKV), human parainfluenza virus 3 (HPIV3), and human herpes virus 6 (HHV6). This hVST product was tolerated in 5 adult and 9 pediatric patients with toxicities limited to grade I-II cytokine release syndrome (n=2), immune effector cell-associated neurotoxicity syndrome (n=1) and chronic GVHD (n=1). Three months post-treatment, 8/8 evaluable patients with active viral infections achieved a partial or complete response to at least one target virus. Single cell gene expression of hVST products showed CD4+ and CD8+ T cells with effector memory and activation markers (n=4). In evaluable recipients (n=4) following hVST infusion, there was a shift from a naïve and indistinct T cell profile pre infusion to predominantly memory T cell populations in the peripheral blood after hVST infusion (median 70 days). These data suggest that hexaviral specific T cells have potential for preventing and treating multiple viruses in patients post-HCT.