IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8 + T Cells

• DOI: 10.1073/pnas.0307298101
• Publication Date: 2004-02-17T20:32:02Z
• Authors: Christopher A. Kl...; Steven E. Finkels...; Deborah R. Surman; Michael K. Lichtman; Luca Gattinoni; Marc R. Theoret; Navrose Grewal; Paul J. Spiess; Paul A. Antony; Douglas C. Palmer; Yutaka Tagaya; Steven A. Rosenberg; Thomas A. Waldmann; Nicholas P. Restifo
• Keywords: Interleukin-15; Mice, Knockout; 0301 basic medicine; Membrane Glycoproteins; Melanoma, Experimental; Receptors, Antigen, T-Cell; Mice, Transgenic; CD8-Positive T-Lymphocytes; Adoptive Transfer; Neoplasm Proteins; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Humans; Interleukin-2; Female; Immunotherapy; Cells, Cultured; gp100 Melanoma Antigen

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.