A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy Journal Article

Authors: Hasan, A. N.; Kollen, W. J.; Trivedi, D.; Selvakumar, A.; Dupont, B.; Sadelain, M.; O'Reilly, R. J.
Article Title: A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy
Abstract: Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8<sup>+</sup>, IFN-γ<sup>+</sup>, and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-γ<sup>+</sup> cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors. Copyright © 2009 by The American Association of Immunologists, Inc.
Keywords: controlled study; genetics; nonhuman; comparative study; cd8 antigen; animal cell; mouse; animal; animals; mice; allele; cells, cultured; alleles; transplantation; virology; biosynthesis; immunology; lymphocyte activation; gamma interferon; cell culture; immunogenicity; immunodominant epitopes; epitope; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; hla antigen class 1; histocompatibility antigens class i; phosphoproteins; effector cell; t-lymphocyte subsets; hla a antigen; hla b antigen; epitopes, t-lymphocyte; cytomegalovirus antigen pp65; intercellular adhesion molecule 1; lymphocyte function associated antigen 3; cytomegalovirus matrix protein 65kda; hla a 0301 antigen; hla a*0201 antigen; hla a2402 antigen; hla b*0702; hla b*0801 antigen; hla-a 0301 antigen; hla-a*0201 antigen; hla-b*0702; hla-b*0801 antigen; matrix protein; phosphoprotein; adoptive immunotherapy; antigen presenting cell; cell expansion; cytomegalovirus; cell strain 3t3; t lymphocyte subpopulation; hla-a antigens; hla-b antigens; immunotherapy, adoptive; nih 3t3 cells; viral matrix proteins
Journal Title: Journal of Immunology
Volume: 183
Issue: 4
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2009-08-15
Start Page: 2837
End Page: 2850
Language: English
DOI: 10.4049/jimmunol.0804178
PUBMED: 19635907
PROVIDER: scopus
PMCID: PMC3079474
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Wouter Jan Willem Kollen
    7 Kollen
  2. Deepa Trivedi
    14 Trivedi
  3. Michel W J Sadelain
    538 Sadelain
  4. Aisha Nasreen Hasan
    53 Hasan
  5. Richard O'Reilly
    707 O'Reilly
  6. Bo Dupont
    252 Dupont