Comparable anti-CMV responses of transplant donor and third-party CMV-specific T cells for treatment of CMV infection after allogeneic stem cell transplantation

• Published in: Cellular & molecular immunology 2022-04, Vol.19 (4), p.482-491
• Main 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
• Format: Article
• Language: English
• Subjects: 631/250/1904; 631/250/254; Adoptive transfer; Animal models; Animals; Antibodies; Antiviral activity; Biomedical and Life Sciences; Biomedicine; CD8 antigen; Cell proliferation; Cytomegalovirus; Cytomegalovirus Infections; Cytotoxicity; Donors; Hematopoietic Stem Cell Transplantation; Humans; Immunology; Infections; Lymphocytes T; Medical Microbiology; Mice; Microbiology; Stem Cell Transplantation; T-Lymphocytes, Cytotoxic; Third party; Tissue Donors; Tumors; Vaccine
• ISSN: 2042-0226; 1672-7681; 2042-0226
• DOI: 10.1038/s41423-021-00829-y

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.