title: Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice.
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: Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors: J A
authors: JA
authors: Westwood
authors: W K
authors: WK
authors: Murray
authors: M
authors: M
authors: Trivett
authors: A
authors: A
authors: Shin
authors: P
authors: P
authors: Neeson
authors: D P
authors: DP
authors: MacGregor
authors: N M
authors: NM
authors: Haynes
authors: J A
authors: JA
authors: Trapani
authors: P
authors: P
authors: Mayura-Guru
authors: S
authors: S
authors: Fox
authors: S
authors: S
authors: Peinert
authors: D
authors: D
authors: Honemann
authors: H M
authors: HM
authors: Prince
authors: D
authors: D
authors: Ritchie
authors: A M
authors: AM
authors: Scott
authors: F E
authors: FE
authors: Smyth
authors: M J
authors: MJ
authors: Smyth
authors: P K
authors: PK
authors: Darcy
authors: M H
authors: MH
authors: Kershaw
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002472:Cell Transformation, Viral; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000008:administration & dosage*; D007938:Leukemia / Q000821:virology; D008223:Lymphoma / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000637:transplantation / Q000821:virology*; D013995:Time; D014161:Transduction, Genetic / Q000379:methods; D019076:Transgenes