Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice Academic Article uri icon

abstract

  • There is considerable concern regarding the transforming potential of retroviral vectors currently used for gene therapy, with evidence that retroviral integration can lead to leukemia in recipients of gene-modified stem cells. However, it is not clear whether retroviral-mediated transduction of T cells can lead to malignancy. We transduced mouse T cells with a Moloney murine retroviral gene construct and transferred them into congenic mice, which were preconditioned to enhance the engraftment of transferred T cells. Recipients were then observed long-term for evidence of cancer. Transferred T cells persisted in mice throughout life at levels up to 17% with gene copy numbers up to 5.89 x 10(5) per million splenocytes. Mice receiving gene-modified T cells developed tumors at a similar rate as control mice that did not receive T cells, and tumors in both groups of mice were of a similar range of histologies. Hematological malignancies comprised approximately 60% of cancers, and the remaining cancers consisted largely of carcinomas. Importantly, the incidence of lymphomas was similar in both groups of mice, and no lymphomas were found to be of donor T-cell origin. This study indicates that the use of retroviral vectors to transduce T cells does not lead to malignant transformation.

authors

  • Westwood, JA
  • Murray, WK
  • Trivett, M
  • Shin, A
  • Neeson, P
  • MacGregor, DP
  • Haynes, NM
  • Trapani, JA
  • Mayura-Guru, P
  • Fox, S
  • Peinert, S
  • Honemann, D
  • Prince, HM
  • Ritchie, D
  • Scott, AM
  • Smyth, FE
  • Smyth, MJ
  • Darcy, PK
  • Kershaw, MH

publication date

  • July 2008