Molecular Therapy
Volume 17, Issue 5, May 2009, Pages 880-888
Journal home page for Molecular Therapy

Original Article
Genetic Manipulation of Tumor-specific Cytotoxic T Lymphocytes to Restore Responsiveness to IL-7

https://doi.org/10.1038/mt.2009.34Get rights and content
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Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) can induce objective clinical responses in patients with malignant diseases. The option of providing a proliferative and survival advantage to adoptively transferred CTLs remains a challenge to improve their efficacy. Host lymphodepletion and administration of recombinant interleukin-2 (IL-2) are currently used to improve CTL survival and expansion after adoptive transfer, but these approaches are frequently associated with significant side effects and may increase proliferation of T regulatory cells. IL-7 is a crucial homeostatic cytokine that has been safely administered as a recombinant protein. However, while IL-7 induces robust expansion of naive and memory T lymphocytes, the lack of expression of the IL-7 receptor α chain (IL-7Rα) by CTLs precludes their response to this cytokine. We found that CTLs can be genetically modified to re-express IL-7Rα, and that this manipulation restores the response of these cells to IL-7 without apparent modification of their antigen specificity or dependency, and without changing their response to other common γ (γc) chain cytokines. This approach may allow selective expansion of CTLs without the unwanted effects associated with IL-2.

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published online 03 March 2009