Outcomes with third-party virus-specific T cells after the use of single-antigen cell lines to predict HLA restriction

Patients with significant T-cell dysfunction from chemotherapy or hematopoietic stem cell transplant are at significant risk for complications of viral infections. Off-the-shelf third-party virus-specific T cells (TP VSTs) are an effective and well-tolerated treatment for the management of infection with adenovirus, BK polyomavirus, cytomegalovirus, and Epstein-Barr virus. TP VST product selection for any particular patient incorporates maximizing the number of HLA matches between the product and the patient, along with consideration of the antiviral activity of the product. We have previously shown that single-antigen cell lines (SALs), cell lines expressing a single HLA molecule, can be used in a flow cytometric-based assay to determine sites of HLA restriction for TP VST products. We hypothesized that incorporating match at sites of HLA restriction into TP VST product selection would improve response rates. Here we report on 25 patients who received TP VSTs for the treatment of 26 viral infections with at least 1 match at an HLA-restricted site. In this cohort, the overall response rate was 96.2%, with a complete response rate of 69.2%. These data suggest the annotation of VST banks to include SAL-derived HLA restriction could lead to improved product selection and efficacy. This trial was registered at www.clinicaltrials.gov as #NCT02532452.