Comparison of Transplant Donor- and Third-Party Donor-Derived CMV-Specific T Cells for CMV Infection After Allogenic Stem Cell Transplantation

Abstract

Background: Adoptive transfer of cytomegalovirus (CMV)-specific T cells (CTLs) from original transplant donors or third-party donors was effective for CMV infection after allogenic stem cell transplantation (allo-SCT), but the safety and antiviral activity of CTL types have not been compared. Additionally, mechanisms driving sustained antiviral immunity induced by these CTLs need to be established and compared. \n \nMethods: i) We compared antiviral abilities of transplant donor and third-party CTLs for CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity and analyzed underlying mechanisms driving sustained antiviral immunity induced by these CTLs therapies. ii) We collected data from 31 patients receiving third-party CTLs and selected matched pairs of 62 individuals who received donor CTLs for refractory CMV infection after allo-SCT, compared the safety and efficacy of the CTLs types for CMV infection, and evaluated the recovery of virus-specific immunity in patients. \n \nFindings: i) In mouse models, we observed that both donor and third-party CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days post-infusion. The in vivo recovery of CMV-specific immunity after CTLs infusion was comparable in both groups. A detailed analysis of the source of recovered CTLs showed the proliferation and expansion of graft-derived endogenous CTLs in both groups. ii) In patients, adoptive therapy with donor or third-party CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8 + tetramer + T cells and the proliferation of recipient’s endogenous CTLs after CTLs infusion, which were associated with a reduced or cleared of viral load. \n \nInterpretation: Adoptive therapy with transplant donor or third-party CTLs triggered comparable antiviral responses to CMV infection by helping to restore CMV-specific immunity. \n \nFunding: National Key Research and Development Program of China, National Natural Science Foundation of China. \n \nDeclaration of Interest: The authors have no competing financial interests to declare. \n \nEthical Approval: This study was approved by the ethics committee of Peking University People s Hospital