Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent


30 Sep 2019


Poster Display session 3



Tumour Site


Kristin Hicks


Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253


K.C. Hicks, K.M. Knudson, Y. Ozawa, J. Schlom, S.R. Gameiro

Author affiliations

  • Laboratory Of Tumor Immunology And Biology, Center for Cancer Research, National Cancer Institute, 20892 - Bethesda/US


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 1802


Targeting programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has failed to provide durable clinical benefit for a majority of patients with solid carcinomas. Recent preclinical and clinical data suggests that addition of the IL-15 superagonist N-803 improves response rates to anti-PD-1 or anti-PD-L1 therapy. Thus, we hypothesized that N-809, a novel bifunctional agent comprised of N-803 fused to two single chain anti-PD-L1 variable region domains, would promote potent anti-tumor efficacy and immune activation in murine models of solid carcinomas.


The functionality of the N-809 components was examined in vitro. Anti-tumor efficacy of N-809 versus a clinically relevant dose of N-803 + anti-PD-L1 was assessed using murine MC38 colon and 4T1 triple negative breast tumor models. The immune-mediated mechanism of N-809 was examined in spleen and tumor using comprehensive flow-based analyses and functional assays. Serum cytokine levels were also measured. Finally, effects on tumor gene expression were examined using Nanostring. Nant biosciences provided N-809 as per Cooperative Research and Development Agreement with NCI.


In vitrostudies confirmed that both components of N-809 were functional. N-809 drastically reduced MC38 tumor burden leading to increased survival and significantly reduced spontaneous lung metastasis of 4T1 tumors. In both tumor models, N-809 had improved efficacy versus a clinically relevant dose of N-803 + anti-PD-L1. In the MC38 model, N-809 increased serum levels of IFNg, TNFa, and IL-10. Depletion studies revealed that CD8+T and NK cells are required for the anti-tumor efficacy of N-809. The immune analysis showed enhanced CD8+ T and NK cell tumor infiltration, activation, and function. To determine the mechanism of the increased CD8 and NK cell infiltration, analyses were performed to examine tumor chemokines and inhibition of immune cell migration. Gene analysis revealed changes in chemokines, chemokine receptors, and immune response genes.


N-809 has anti-tumor efficacy in two murine carcinoma model mediated by increasing the number, activation, and function of CD8+ T cells and NK cells.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.


Nant Bioscience.


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.