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Ex vivo expansion of human cytomegalovirus‐specific cytotoxic T cells by recombinant polyepitope: implications for HCMV immunotherapy
Author(s) -
Rist Michael,
Cooper Leanne,
Elkington Rebecca,
Walker Susan,
Fazou Chrysa,
Tellam Judy,
Crough Tania,
Khanna Rajiv
Publication year - 2005
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200425746
Subject(s) - biology , epitope , human cytomegalovirus , immunology , antigen , cytotoxic t cell , virology , immunotherapy , immune system , t cell , virus , in vitro , biochemistry
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.