Immunotherapy with donor T cells sensitized with overlapping pentadecapeptides for treatment of persistent cytomegalovirus infection or viremia Journal Article

Authors: Koehne, G.; Hasan, A.; Doubrovina, E.; Prockop, S.; Tyler, E.; Wasilewski, G.; O'Reilly, R. J.
Article 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 V<inf>β</inf> 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. © 2015 American Society for Blood and Marrow Transplantation.
Keywords: adult; clinical article; controlled study; middle aged; unclassified drug; allele; in vitro study; amino acid sequence; antigen specificity; hla antigen class 2; epitope mapping; epitope; hla antigen class 1; graft versus host reaction; persistent virus infection; allogeneic hematopoietic stem cell transplantation; adoptive transfer; methylprednisolone; phase 1 clinical trial; t cell depletion; cyclosporin a; cytomegalovirus infection; cytomegalovirus antigen pp65; adoptive immunotherapy; polypeptide; viremia; viral clearance; overlapping pentadecapeptides; lymphocyte transfer; mycophenolate mofetil; pentadecapeptide; human; article; epitope-specific and hla-restricted t cell responses; persistent cytomegalovirus (cmv) infection
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 21
Issue: 9
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2015-09-01
Start Page: 1663
End Page: 1678
Language: English
DOI: 10.1016/j.bbmt.2015.05.015
PROVIDER: scopus
PMCID: PMC4537838
PUBMED: 26028505
Notes: Export Date: 2 September 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Susan E Prockop
    254 Prockop
  2. Guenther Koehne
    194 Koehne
  3. Aisha Nasreen Hasan
    55 Hasan
  4. Richard O'Reilly
    719 O'Reilly
  5. Eleanor M Tyler
    9 Tyler