Article

Immunologic Research

, Volume 42, Issue 1, pp 166-181

Genetic engineering of T cells for adoptive immunotherapy

  • Angel Varela-RohenaAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Carmine CarpenitoAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Elena E. PerezAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Max RichardsonAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Richard V. ParryAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Michael MiloneAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , John SchollerAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Xueli HaoAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
  • , Angela MexasAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
    • , Richard G. CarrollAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
    • , Carl H. JuneAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania
    • , James L. RileyAffiliated withDepartment of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania Email author 

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Abstract

To be effective for the treatment of cancer and infectious diseases, T cell adoptive immunotherapy requires large numbers of cells with abundant proliferative reserves and intact effector functions. We are achieving these goals using a gene therapy strategy wherein the desired characteristics are introduced into a starting cell population, primarily by high efficiency lentiviral vector-mediated transduction. Modified cells are then expanded using ex vivo expansion protocols designed to minimally alter the desired cellular phenotype. In this article, we focus on strategies to (1) dissect the signals controlling T cell proliferation; (2) render CD4 T cells resistant to HIV-1 infection; and (3) redirect CD8 T cell antigen specificity.

Keywords

Lentiviral vector CD28 PD-1 TCR Chimeric immunoreceptor Zinc-finger nuclease NOG mice Immunotherapy Adoptive T cell therapy