Expansion of cytomegalovirus pp65 and IE-1 specific cytotoxic T lymphocytes for cytomegalovirus-specific immunotherapy following allogeneic stem cell transplantation.
Adoptive immunotherapy with antigen-specific cytotoxic T lymphocytes (CTLs) has proven effective in restoring cellular immunity to cytomegalovirus (CMV) and preventing viral reactivation after allogeneic stem cell transplantation (SCT). In an effort to develop a cost-effective, relatively rapid method of CMV CTL expansion, we investigated the use of a pool of overlapping CMV peptides. Because the possibility exists of vaccinating CMV-seronegative donors, and these individuals may have T cell responses predominantly against IE-1, commercially available peptide mixes for pp65 as well as IE-1 were used to stimulate CTLs from 10 seropositive donors. Of these 10 donors, 4 responded to pp65 only, 1 did not respond to either pp65 or IE-1, 4 responded to both pp65 and IE-1, and 1 responded to IE-1 only. These CMV- specific T cells included a mixture of CD4(+) and CD8(+) effectors, and specific cytotoxicity correlated with interferon-gamma production. The costs associated with a 28-day maintenance course of intravenous ganciclovir, cidofovir, foscarnet, and valganciclovir, as well as the preparation and shipping a single dose of CTLs, were determined. The price of generating CMV CTLs using this method was comparable to or less expensive than a 28-day maintenance course for these agents, not including the costs associated with drug administration, supportive care, and the treatment of drug-related complications. Considering the relative ease, low cost, and the fact that CTL administration can result in CMV-specific immune reconstitution, this option should be considered for patients with CMV reactivation or for prophylaxis in patients at high risk for infection.
Bao
Lei
L
Department of Pediatrics, Division of Hematology-Oncology, Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
Dunham
Kimberly
K
Department of Pediatrics, Division of Hematology-Oncology, Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
Stamer
Mindy
M
Department of Pediatrics, Division of Hematology-Oncology, Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
Mulieri
Kevin M
KM
Department of Pharmacy, and Pharmacology Medicine, Penn State Hershey Children's Hospital, Hershey, Pennsylvania.
Lucas
Kenneth G
KG
Department of Pediatrics, Division of Hematology-Oncology, Penn State Hershey Children's Hospital, Hershey, Pennsylvania. Electronic address: klucas@psu.edu.
D000956:Antigens, Viral / Q000276:immunology / Q000627:therapeutic use*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000628:therapy*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
D000956:Antigens, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa