| Title | Comparable anti-CMV responses of transplant donor and third-party CMV-specific T cells for treatment of CMV infection after allogeneic stem cell transplantation |
| Authors | Pei, Xu-Ying Liu, Xue-Fei Zhao, Xiang-Yu Lv, Meng Mo, Xiao-Dong Chang, Ying-Jun Shang, Qian-Nan Sun, Yu-Qian Chen, Yu-Hong Xu, Lan-Ping Wang, Yu Zhang, Xiao-Hui Liu, Kai-Yan Huang, Xiao-Jun |
| Affiliation | Peking Univ, Peking Univ Peoples Hosp, Inst Hematol, Natl Clin Res Ctr Hematol Dis,Beijing Key Lab Hem, Beijing 100044, Peoples R China Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China |
| Keywords | CYTOMEGALOVIRUS-INFECTION VIRAL-INFECTIONS ADOPTIVE TRANSFER IMMUNOTHERAPY LYMPHOCYTES RECONSTITUTION IMMUNITY THERAPY RECIPIENTS CD4(+) |
| Issue Date | Jan-2022 |
| Publisher | CELLULAR & MOLECULAR IMMUNOLOGY |
| Abstract | Adoptive transfer of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation (allo-SCT), but the antiviral activity of CMV-CTL types has not been compared. To determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs, we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity, and analyzed the underlying mechanisms driving sustained antiviral immunity. The results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days postinfusion. The in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups. A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both groups. Our clinical study, which enrolled 31 patients who received third-party CMV-CTLs and 62 matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection, further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8(+) tetramer(+) T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion, which were associated with a reduced or cleared viral load. Our data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity. |
| URI | http://hdl.handle.net/20.500.11897/634762 |
| ISSN | 1672-7681 |
| DOI | 10.1038/s41423-021-00829-y |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
