Abstract 39P
Background
ANV419 is an antibody-cytokine fusion protein with natural affinity to the heterodimeric IL-2Rβ/γ, but no affinity for IL-2Rα. Therefore, ANV419 preferentially stimulates CD8 T cells and NK cells over regulatory T cells. ANV419 is currently being investigated in a phase I/II dose finding study in patients with solid tumors. Goal of the presented study was the evaluation of the activity of ANV419 on NK cells and its potential combination with complementary immune-oncology mechanisms that can strengthen its NK or CD8 T cell anti-tumor response for the planned phase II trials.
Methods
The signaling properties and effects of ANV419 on NK cell receptor expression were compared to IL-2 and IL-15 in human PBMCs. NK cell killing was analyzed in combination with trastuzumab in vitro and in the N87 xenograft mouse model. Combination of ANV419 with checkpoint inhibitors was tested in the H22 syngeneic tumor mouse model.
Results
In NK cells, ANV419 showed STAT5 phosphorylation kinetics and NK receptor regulation that was comparable to recombinant IL-2 and IL-15. In vitro combination of ANV419 with the antibody dependent cellular cytotoxicity (ADCC) inducing anti-HER2 antibody trastuzumab showed additive effects in NK cell killing compared to single trastuzumab treatment. In line with the in vitro findings, the combination of trastuzumab and ANV419 exhibited additive effects in the N87 xenograft model supporting clinical combination of ANV419 with treatments fostering NK cell mediated killing. To assess the role of ANV419 in indications where T cells are involved in tumor resolution, ANV419 combination with the checkpoint inhibitors anti-PD1 or anti-CTLA4 was tested and showed additive effects in tumor growth retardation in mice bearing H22 tumors compared to single treated mice.
Conclusions
The data presented here, support the initiation of clinical phase II studies assessing ANV419 treatment in indications in which NK and CD8 T cells are involved in tumor resolution and in combination with ADCC inducing treatments or checkpoint inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Anaveon AG.
Funding
Syncona, Novartis Venture Fund, Forbion, Cowen Healthcare investments, Pfizer Ventures, Pontifax, UZH Life Sciences Fund, BaseLaunch.
Disclosure
All authors have declared no conflicts of interest.