Confirmation of High Resolution Antiviral HLA Restrictions Correlates with Antiviral Responses Following Virus-Specific T-Cell Therapy
Year: 2019
Type: article
Study design: Observational Study
Abstract: Background Adoptive immunotherapy using virus-specific T-lymphocytes (VSTs) have been successful in treating viral infections in immunocompromised patients, and use of VSTs from healthy third-party donors have improved the accessibility and timeliness of this therapy. However, best methods of donor/recipient matching of HLA-mismatched VST products remain unclear. Objective To determine the factors influencing the chances of antiviral responses following VST therapy between HLA-mismatched donor/recipient pairs. Design/Methods Patients who received HLA-mismatched VST infusions for active infections with CMV, Epstein-Barr virus, or adenovirus were analyzed for response. Antiviral response was defined as >1 log decrease in viral load within 3 months of VST infusion. Degree of high and low resolution HLA match was determined, and presence of confirmed antiviral HLA restrictions in the utilized VST products was recorded. Unpaired, 2-tailed T-tests were performed for group comparisons. Results Twenty one patients received 30 VST infusions with 27 T-cell products (20 from third-party donors, and 7 from mismatched related donors). Eleven patients were treated for CMV, 8 for adenovirus, and 2 for EBV infection. All patients had persistent viral infections in spite of standard antiviral therapy prior to study enrollment. Seven patients were admitted to intensive care units due to severe viral disease and received VSTs under expanded access for emergency treatment. Overall, of this poor prognosis patient cohort, 12 achieved antiviral responses within 3 months of infusion (2 of 7 patients who received VST derived from MMRD, and 10 of 20 patients who received third-party VSTs). Of 25 evaluable infusions, chances of antiviral response following VST infusion were greater when utilizing a VST product with a confirmed antiviral HLA restriction that is shared at high resolution with the recipient (p=0.02). There was no difference in overall degree of HLA match between responders and non-responders (p=0.83). Conclusions VST matching based on sharing of high resolution HLA alleles that mediate target antiviral restrictions is more successful than overall degree of HLA match. Further testing of this methodology for VST therapy is ongoing in a current phase II trial (PBMTC SUP1701).
Institution: Children's National
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2911441962