title: IL-12 conditioning improves retrovirally mediated transduction efficiency of CD8+ T cells.
abstract: The ability to genetically modify T cells is a critical component to many immunotherapeutic strategies and research studies. However, the success of these approaches is often limited by transduction efficiency. As retroviral vectors require cell division for integration, transduction efficiency is dependent on the appropriate activation and culture conditions for T cells. Naive CD8(+) T cells, which are quiescent, must be first activated to induce cell division to allow genetic modification. To optimize this process, we activated mouse T cells with a panel of different cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-12, IL-15 and IL-23, known to act on T cells. After activation, cytokines were removed, and activated T cells were retrovirally transduced. We found that IL-12 preconditioning of mouse T cells greatly enhanced transduction efficiency, while preserving function and expansion potential. We also observed a similar transduction-enhancing effect of IL-12 preconditioning on human T cells. These findings provide a simple method to improve the transduction efficiencies of CD8(+) T cells.
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Andrijauskaite
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Suriano
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Cloud
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kesarwani
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Stefanik
authors.affiliation: Loyola University Chicago, Maywood, IL, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Moxley
authors.affiliation: Immunology and Biotechnology Division, Faculty of Science, Tanta University, Tanta, Egypt.
authors.forename: M L
authors.initials: ML
authors.lastname: Salem
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: E
authors.initials: E
authors.lastname: Garrett-Mayer
authors.affiliation: 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Paulos
authors.affiliation: 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Experimental Transplantation and Immunology Branch , National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Kochenderfer
authors.affiliation: 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.affiliation: 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Rubinstein
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D018664:Interleukin-12