TY - JOUR
T1 - IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8 + T Cells
AU - Klebanoff, Christopher A.
AU - Finkelstein, Steven E.
AU - Surman, Deborah R.
AU - Lichtman, Michael K.
AU - Gattinoni, Luca
AU - Theoret, Marc R.
AU - Grewal, Navrose
AU - Spiess, Paul J.
AU - Antony, Paul A.
AU - Palmer, Douglas C.
AU - Tagaya, Yutaka
AU - Rosenberg, Steven A.
AU - Waldmann, Thomas A.
AU - Restifo, Nicholas P.
PY - 2004/2/17
Y1 - 2004/2/17
N2 - IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+ memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+ T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+ T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+ T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8 + T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.
AB - IL-15 and IL-2 possess similar properties, including the ability to induce T cell proliferation. However, whereas IL-2 can promote apoptosis and limit CD8+ memory T cell survival and proliferation, IL-15 helps maintain a memory CD8+ T cell population and can inhibit apoptosis. We sought to determine whether IL-15 could enhance the in vivo function of tumor/self-reactive CD8+ T cells by using a T cell receptor transgenic mouse (pmel-1) whose CD8+ T cells recognize an epitope derived from the self/melanoma antigen gp100. By removing endogenous IL-15 by using tumor-bearing IL-15 knockout hosts or supplementing IL-15 by means of exogenous administration, as a component of culture media or as a transgene expressed by adoptively transferred T cells, we demonstrate that IL-15 can improve the in vivo antitumor activity of adoptively transferred CD8 + T cells. These results provide several avenues for improving adoptive immunotherapy of cancer in patients.
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U2 - 10.1073/pnas.0307298101
DO - 10.1073/pnas.0307298101
M3 - Article
C2 - 14762166
AN - SCOPUS:10744226452
SN - 0027-8424
VL - 101
SP - 1969
EP - 1974
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -