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. Methods: 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. Findings: 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. Interpretation: Adoptive therapy with transplant donor or third-party CTLs triggered comparable antiviral responses to CMV infection by helping to restore CMV-specific immunity. Funding: National Key Research and Development Program of China, National Natural Science Foundation of China. Declaration of Interest: The authors have no competing financial interests to declare. Ethical Approval: This study was approved by the ethics committee of Peking University People's Hospital