Large-Scale Expansion of Dendritic Cell-Primed Polyclonal Human Cytotoxic T-Lymphocyte Lines Using Lymphoblastoid Cell Lines for Adoptive Immunotherapy

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Abstract
Dendritic cells (DCs) have been shown to activate cytotoxic T-lymphocytes (CTLs) for many tumor and virus-associated antigens in vitro. In this study, the authors tested the feasibility of using DCs to expand polyclonal, cytomegalovirus (CMV)-specific CTL lines for adoptive immunotherapy. Two stimulations with DCs expressing pp65, the immunodominant antigen of CMV, effectively activated and expanded MHC-class I restricted, CMV-specific CTLs from peripheral blood mononuclear cells. However, limiting monocyte-derived DC numbers precluded the authors from expanding the CTLs to the numbers required for adoptive transfer protocols. Nonspecific stimulation methods failed to expand CTL lines specifically. However, the authors found that lymphoblastoid cell lines (LCLs) expressing pp65 expanded pp65-specific CTL lines without competition from EBV-specific CTLs. An unlimited source of antigen presenting cells that could present antigen in the appropriate MHC context emerged as a critical point for expansion of polyclonal, antigen-specific CTL lines.