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Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

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IL15N72D superagonist/IL15Rα-Fc fusion complex (ALT-803) exhibits anti-metastatic activity in murine breast tumor model

Interleukin (IL)-15N72D-superagonist-complexed with IL15Rα-Fc fusion protein (IL15-SA/IL15Rα-Fc, also known as ALT-803) has been reported to have greater anti-myeloma activity, due to its increased in vivo half-life and unique tissue biodistribution, than native IL-15 alone in murine models. In order to test the anti-tumor efficacy of IL15-SA/IL15Rα-Fc in a non-hematologic murine cancer model, we examined the monotherapy effect of IL15-SA/IL15Rα-Fc in non-tumor bearing mice and in the 4T1-breast tumor model. In non-tumor bearing Balb/c mice, IL15-SA/IL15Rα-Fc (1 µg i.p.), a 10-fold increase occurred in NK cells followed by CD8+ T cells (3-fold), both peaking on Day 3 post treatment. In examining NK cell population subsets, the greatest significant change was in high effector (CD11b+, CD27hi) NKs as compared with terminal effector (CD11b+, CD27lo) NKs on Day 3 post IL15-SA/IL15Rα-Fc-treatment, leading to increased NK function on a per-cell basis. CD8 subset analysis determined that IL15-SA/IL15Rα-Fc significantly increased IL15-responding, memory (CD122+, CD44+) CD8+ T cells, in particular those having the innate (NKG2D+, PD1-) phenotype. In 4T1 tumor bearing mice, IL15-SA/IL15Rα-Fc induced significant anti-metastatic activity, and thus consequently resulted in a longer median survival of IL15-SA/IL15Rα-Fc-treated mice following surgical resection of the primary tumor. Finally, T cell depletion revealed that the anti-metastatic property of IL15-SA/IL15Rα-Fc was dependent on CD8+ T cells and not CD4+ T cells. Altogether, these studies showed for the first time that IL15-SA/IL15Rα-Fc a) promoted the development of high effector NKs, b) enhanced per-cell function of NKs, and c) played a vital role in reducing tumor metastasis and ultimately survival.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Kim, P.S., Kwilas, A.R., Jeng, E.K. et al. IL15N72D superagonist/IL15Rα-Fc fusion complex (ALT-803) exhibits anti-metastatic activity in murine breast tumor model. j. immunotherapy cancer 3 (Suppl 2), P229 (2015).

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