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PMID: 14762166 Published · ppublish English Journal Article

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 7 ·2004-02-17 ·Pages 1969-74

Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, Grewal N, Spiess PJ, Antony PA, Palmer DC, Tagaya Y, Rosenberg SA, Waldmann TA, Restifo NP

Abstract

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.

MeSH Terms
Adoptive Transfer Animals CD8-Positive T-Lymphocytes/cytology,immunology,metabolism,transplantation Cells, Cultured Female Humans Immunotherapy Interleukin-15/genetics,immunology,pharmacology Interleukin-2/immunology,pharmacology Melanoma, Experimental/immunology Membrane Glycoproteins/immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neoplasm Proteins/immunology Receptors, Antigen, T-Cell/genetics,immunology gp100 Melanoma Antigen
Chemicals
Interleukin-15 Interleukin-2 Membrane Glycoproteins Neoplasm Proteins PMEL protein, human Pmel protein, mouse Receptors, Antigen, T-Cell gp100 Melanoma Antigen
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Klebanoff Christopher A
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA.
Finkelstein Steven E
Surman Deborah R
Lichtman Michael K
Gattinoni Luca
Theoret Marc R
Grewal Navrose
Spiess Paul J
Antony Paul A
Palmer Douglas C
Tagaya Yutaka
Rosenberg Steven A
Waldmann Thomas A
Restifo Nicholas P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307298101
Published
2004-02-17
Epub
2004-00-04
Pages
1969-74
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC357036
Subset
IM
Grants
Intramural NIH HHS · Z01 BC010763-01 · United States
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307298101 PMC Full Text View journal details
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