title: Ex vivo expansion of human cytomegalovirus-specific cytotoxic T cells by recombinant polyepitope: implications for HCMV immunotherapy.
abstract: Stem cell transplantation (SCT) remains the most effective curative therapy for the majority of hematopoietic malignancies. Unfortunately, SCT is limited by its toxicity and infectious complications that result from profound immunosuppression. In particular, acquisition of exogenous or reactivation of endogenous human cytomegalovirus (HCMV) is common after SCT. More recently, reconstitution of host immunity through augmentation of anti-HCMV T cell responses has been proposed as an exciting candidate therapy to avoid the requirement for antiviral drug use. Here we have developed a novel antigen presentation system based on a replication-deficient adenovirus that encodes multiple HLA class I-restricted epitopes from eight different antigens of HCMV as a polyepitope (referred to as AdCMVpoly). Ex vivo stimulation of peripheral blood mononuclear cells with AdCMVpoly consistently showed rapid stimulation and expansion of multiple epitope-specific T cells that recognized endogenously processed epitopes presented on virus-infected cells. Interestingly, the AdCMVpoly expression system is capable of expanding antigen-specific T cells even in the absence of CD4(+) T cells. These studies show the effectiveness of a polyepitope antigen presentation system for reproducible expansion of antigen-specific T cells from immunocompetent and immunocompromised settings.
authors.affiliation: Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research and Joint Oncology Program, Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Rist
authors.forename: Leanne
authors.initials: L
authors.lastname: Cooper
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elkington
authors.forename: Susan
authors.initials: S
authors.lastname: Walker
authors.forename: Chrysa
authors.initials: C
authors.lastname: Fazou
authors.forename: Judy
authors.initials: J
authors.lastname: Tellam
authors.forename: Tania
authors.initials: T
authors.lastname: Crough
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007158:Immunologic Techniques; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins