title: Immunotherapy with Donor T Cells Sensitized with Overlapping Pentadecapeptides for Treatment of Persistent Cytomegalovirus Infection or Viremia.
abstract: We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadecapeptides (15-mer peptides) spanning the sequence of CMVpp65 for adoptive therapy of 17 allogeneic hematopoietic cell transplant recipients with cytomegalovirus (CMV) viremia or clinical infection persisting despite prolonged treatment with antiviral drugs. All but 3 of the patients had received T cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis with immunosuppressive drugs after transplantation. The CMVpp65-specific T cells (CMVpp65CTLs) generated were oligoclonal and specific for only 1 to 3 epitopes, presented by a limited set of HLA class I or II alleles. T cell infusions were well tolerated without toxicity or GVHD. Of 17 patients treated with transplant donor (n = 16) or third-party (n = 1) CMVpp65CTLs, 15 cleared viremia, including 3 of 5 with overt disease. In responding patients, the CMVpp65CTLs infused consistently proliferated and could be detected by T cell receptor Vβ usage in CMVpp65/HLA tetramer + populations for period of 120 days to up to 2 years after infusion. Thus, CMVpp65CTLs generated in response to synthetic 15-mer peptides of CMVpp65 are safe and can clear persistent CMV infections in the post-transplantation period.
authors.affiliation: Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York. Electronic address: koehneg@mskcc.org.
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
authors.affiliation: Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Aisha
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Doubrovina
authors.affiliation: Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Prockop
authors.affiliation: Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Tyler
authors.affiliation: Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Gloria
authors.initials: G
authors.lastname: Wasilewski
authors.affiliation: Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D000368:Aged; D064591:Allografts; D002648:Child; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D010750:Phosphoproteins / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D014019:Tissue Donors; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000494:pharmacology; D014766:Viremia / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa
keywords: Adoptive immunotherapy; Epitope-specific and HLA-restricted T cell responses; Overlapping pentadecapeptides; Persistent cytomegalovirus (CMV) infection