Retroviral transduction of T lymphocytes for suicide gene therapy in allogeneic stem cell transplantation

Bone Marrow Transplant. 2000 May:25 Suppl 2:S96-8. doi: 10.1038/sj.bmt.1702364.

Abstract

Transplantation of suicide gene modified allogeneic T lymphocytes is an approach to prevent T cell mediated GVHD while preserving the 'graft-versus-leukemia' (GVL) effect of an allograft. A prerequisite for such a therapy is the efficient transduction of T cells with suitable vectors. Since existing techniques allow only insufficient transduction of T cells, the development of more efficient gene transfer protocols into these cells is of great importance. We present here a protocol for the highly efficient transduction of human primary T cells at high densities (1 x 10(6) cells/ml) by retroviral infection. The presented protocol allowed us to obtain transduction rates of more than 70% of CD3+ cells after two cycles of infection. It is based on the use of FBS-free media for both the production of retrovirus-containing supernatant, as well as the cultivation of the primary T cells. Since the protocol presented here works just as efficiently under large scale conditions, it may easily be adapted to clinical needs and 'good manufacturing practice' (GMP) standards.

MeSH terms

  • Fibronectins
  • Genetic Therapy / methods*
  • Graft vs Host Disease / prevention & control
  • Graft vs Leukemia Effect
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • In Vitro Techniques
  • Retroviridae / genetics*
  • T-Lymphocytes / virology*
  • Transduction, Genetic*
  • Transplantation, Homologous

Substances

  • Fibronectins