Genetic Modification of T Cells With IL-21 Enhances Antigen Presentation and Generation of Central Memory Tumor-specific Cytotoxic T-lymphocytes

• DOI: 10.1097/cji.0b013e3181ad4071
• Publication Date: 2009-07-17T07:24:09Z
• Authors: Anjum S. Kaka; Donald R. Shaffer; Ryan Hartmeier; Ann M. Leen; An Lu; Adham Bear; Cliona M. Rooney; Aaron E. Foster
• Keywords: CTL*; Tumor Antigen

An optimized antigen-presenting cell for tumor immunotherapy should produce a robust antigen specific cytotoxic T lymphocytes (CTL) response to tumor-associated antigens, which can persist in vivo and expand on reencounter. Interleukin (IL)-21 synergizes with other γ-chain cytokines enhance the frequency cytotoxicity of antigen-specific CTL. As cells themselves may serve as effective (T cells; TAPC) be useful cellular vaccines, we examined whether CD8+ genetically modified IL-21 could induce immune responses associated peptides healthy human leukocyte antigen-A2+ donors. We found that TAPC enhanced both proliferation survival MART-1 cells, were enriched by >8-fold over cultures control nontransgenic TAPC. MART-1-specific CTL produced interferon-γ cognate peptide killed primary expressing major histocompatibility complex restricted manner. similarly generation functional against melanoma gp100 B-cell chronic lymphocytic leukemia RHAMM antigen. Antigen-specific generated using gene-modified had central memory phenotype characterized CD45RA–, CD44high, CD27high, CD28high, CD62Lhigh, IL-7 receptor-αhigh, contrasting terminal effector absence IL-21. Thus, stimulation presences enhances favors induction phenotype, improve proliferation, survival, efficacy T-cell based therapies treatment cancer.