Generation and infusion of multi-antigen-specific T cells to prevent complications early after T-cell depleted allogeneic stem cell transplantation—a phase I/II study

• Published in: Leukemia Vol. 34; no. 3; pp. 831 - 844
• Main Authors: Roex, Marthe C. J., van Balen, Peter, Germeroth, Lothar, Hageman, Lois, van Egmond, Esther, Veld, Sabrina A. J., Hoogstraten, Conny, van Liempt, Ellis, Zwaginga, Jaap J., de Wreede, Liesbeth C., Meij, Pauline, Vossen, Ann C. T. M., Danhof, Sophia, Einsele, Hermann, Schaafsma, M. Ron, Veelken, Hendrik, Halkes, Constantijn J. M., Jedema, Inge, Falkenburg, J. H. Frederik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2020; Nature Publishing Group
• Subjects: 13/1; 13/31; 631/250/1904; 631/250/251; 631/67/1990; 692/308/2779/109/1940; 692/308/575; Adenoviridae Infections - prevention & control; Adult; Aged; Antigen (tumor-associated); Antigens; Antigens, Neoplasm - immunology; Cancer Research; CD8-Positive T-Lymphocytes - cytology; Complications; Critical Care Medicine; Cytomegalovirus; Cytomegalovirus Infections - prevention & control; Depletion; Epstein-Barr virus; Epstein-Barr Virus Infections - prevention & control; Expansion; Feasibility Studies; Female; Graft-versus-host reaction; Health aspects; Hematologic Neoplasms - complications; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Hematology; Histocompatibility antigen HLA; Humans; Immunotherapy; Intensive; Internal Medicine; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; Medical treatment; Medicine; Medicine & Public Health; Middle Aged; Minor histocompatibility antigens; Minor Histocompatibility Antigens - immunology; Oncology; Patient Safety; Prevention; Stem Cell Transplantation; Stem cells; T cells; T-Lymphocytes - immunology; Transplantation; Transplantation, Homologous; Viral diseases; Virus diseases; Viruses; Netherlands
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-019-0600-z

Prophylactic infusion of selected donor T cells can be an effective method to restore specific immunity after T-cell-depleted allogeneic stem cell transplantation (TCD-alloSCT). In this phase I/II study, we aimed to reduce the risk of viral complications and disease relapses by administrating donor-derived CD8 pos T cells directed against cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus antigens, tumor-associated antigens (TAA) and minor histocompatibility antigens (MiHA). Twenty-seven of thirty-six screened HLA-A*02:01 pos patients and their CMV pos and/or EBV pos donors were included. Using MHC-I- Strep tamers, 27 T-cell products were generated containing a median of 5.2 × 10 6 cells. Twenty-four products were administered without infusion-related complications at a median of 58 days post alloSCT. No patients developed graft-versus-host disease during follow-up. Five patients showed disease progression without coinciding expansion of TAA/MiHA-specific T cells. Eight patients experienced CMV- and/or EBV-reactivations. Four of these reactivations were clinically relevant requiring antiviral treatment, of which two progressed to viral disease. All resolved ultimately. In 2/4 patients with EBV-reactivations and 6/8 patients with CMV-reactivations, viral loads were followed by the expansion of donor-derived virus target-antigen-specific T cells. In conclusion, generation of multi-antigen-specific T-cell products was feasible, infusions were well tolerated and expansion of target-antigen-specific T cells coinciding viral reactivations was illustrated in the majority of patients.