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Discordant Gene Expression in Adoptively Transferred Retrovirally Modified T Cells

Strategic Insights

— 2 min read

Adoptively transferred retrovirally modified T cells hold promise in the treatment of select cancers, but their efficacy is hindered by the persistent problem of attaining long-term and multi-gene retroviral expression in vivo. A study by M.P. Rubinstein and colleagues at the University of California found that in vitro assays are poor indicators of in vivo efficacy, and that discordant gene expression, characterized by the selective loss of one TCR subunit gene, is associated with the loss of antitumor immunity. This study highlights the need for careful consideration in the design, evaluation, and application of retroviral vectors for cancer treatment.

Key Takeaways:

  • Adoptively transferred retrovirally modified T cells face significant challenges in achieving long-term and multi-gene retroviral expression in vivo.
  • In vitro assays are inadequate for predicting in vivo efficacy, and may lead to misleading conclusions about the effectiveness of retroviral vectors.
  • Discordant gene expression, characterized by the selective loss of one TCR subunit gene, is a major obstacle to antitumor immunity in adoptively transferred T cells.
  • Rubinstein and colleagues demonstrated that genetically modified T cells persisted for over 9 months in a nonlymphopenic environment, but exhibited discordant retrovirally mediated gene expression in vivo.
  • The study suggests that careful consideration is needed in the design, evaluation, and application of retroviral vectors for cancer treatment.
  • M.P. Rubinstein and colleagues' study was published in Cancer Gene Therapy (Loss of T cell-mediated antitumor immunity after construct-specific downregulation of retrovirally encoded T-cell receptor expression in vivo. Cancer Gene Therapy, 2009;16(2):171-183).
  • Rubinstein and colleagues recommend considering the findings of their study to inform the design and application of retroviral vectors.
  • The study has significant implications for the development and application of adoptive T-cell therapy for cancer treatment.

Statistics:

  • The study found that genetically modified T cells persisted for over 9 months in a nonlymphopenic environment.
  • In vitro assays are inadequate for predicting in vivo efficacy, with discordant gene expression occurring in vivo not readily evident from initial in vitro assays.
  • The study revealed that one of the two TCR subunit genes necessary for antigen specificity was selectively lost in vivo.
  • Discordant gene expression was associated with the loss of antitumor immunity in adoptively transferred T cells.

Sources:

  • Cancer Gene Therapy (Loss of T cell-mediated antitumor immunity after construct-specific downregulation of retrovirally encoded T-cell receptor expression in vivo. Cancer Gene Therapy, 2009;16(2):171-183)
  • University of California, Dept. of Biology Science, 9500 Gilman Dr., 0377, La Jolla, CA 92093, USA
  • Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England
  • NewsRx.com
  • Cancer Gene Therapy Week via NewsRx.com

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