title: Genetic modification of cytotoxic T lymphocytes to express cytokine receptors.
abstract: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) or antigen-specific cytotoxic T lymphocytes (CTL) is safe and can be effective in cancer patients. Achievement of clinical responses in these patients is associated with the in vivo expansion and persistence of the transferred T lymphocytes. For this reason, recombinant human interleukin-2 (IL-2) is frequently used to support the in vivo survival of T lymphocytes infused into patients. However, IL-2 also causes important side effects. Thus, alternative strategies are highly demanded to limit cytokine-related off-target effects and to redirect the responsiveness of specific T-cell subsets to selected cytokines. Interleukin-7 (IL-7) is a promising alternative cytokine as it possesses the above mentioned properties. However, because its receptor is downregulated in ex vivo-expanded T cells, methods are required to restore their responsiveness to this homeostatic cytokine. In this chapter, we describe the methodology to obtain the ectopic expression of IL-7 receptor alpha (IL-7Rα) in antigen-specific CTL, using Epstein-Barr virus-specific CTL (EBV-CTL), as a model.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.
authors.forename: Serena K
authors.initials: SK
authors.lastname: Perna
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
mesh_terms: D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival; D018920:Coculture Techniques; D015870:Gene Expression; D005818:Genetic Engineering / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D010766:Phosphorylation; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor