Regulatory Variants of ATF3, CDH17 and FAM71A are Risk Factors for Diisocyanate Induced Occupational Asthma (DA)

Abstract

RATIONALE: Adoptive immunotherapy using virus-specific T-lymphocytes (VSTs) has been successful in treating viral infections after hematopoietic stem cell transplantation (HSCT). Use of partially HLAmatched VSTs from third-party donors allow ''off the shelf'' therapy for viral infections. We hypothesize that third-party VST will be effective and safe in patients with primary immunodeficiency disorders (PID). METHODS: VSTs were cultured from healthy donors via viral pepmix stimulation and expansion. Patients received third party VST infusion before or after HSCT for treatment of CMV, EBV, or adenovirus. Antiviral immunity was assessed via IFNg ELISpot, IFNg capture flow cytometry, and TCRb sequencing. Patients were followed for 45 days following infusion for toxicities and for up to 12 months for antiviral immune reconstitution. RESULTS: Seven patients with PID received 9 VST products at a dose of 2 x 10E7 cells/m2. Four patients had undergone HSCT, while three patients were treated before HSCT due to persistent viral infections. None of the patients developed GVHD, though transient flaring of viral hepatitis occurred in two patients after infusion. Antiviral responses were seen in 5 of 7 patients. Of the pre-HSCT patients, two infants with SCID and cidofovir-refractory adenovirus each received 2 VST infusions and cleared their infections. Expansion of virus-specific T-cells was detectable by IFNg ELIspot or gamma capture in 3 of 5 responding patients. VST persistence was also confirmed by TCRb sequencing in one patient. CONCLUSIONS: Third-party VST are safe in patients with PID, and may be a valuable salvage therapy for the treatment of viral infections before or after HSCT.