NKp46 NKCEs binds to one or two antigens at the surface of tumor cells, and engage both CD16 and NKp46 activating receptors on NK cells. The co-engagement of NKp46 synergizes with CD16 to induce full NK cell activation and tumor cell lysis. Further, NKp46 expression is often conserved on infiltrating NK cells in most solid tumors.
Videos presented in the following scientific conferences:
- European Association of Dermato-Oncology, Paris 2019
- 5th International Conference of Translational Medicine on Pathogenesis and Therapy of Immunomediated Diseases, Milan 2019
NKp46 NKCE: design and Mechanism of action
Video microscopy: NKp46 NKCE
In the scope of the expanded oncology R&D collaboration announced in October 2018, AstraZeneca has recently acquired an option to exclusively license a multi-specific NKp46 NK cell engager from Innate Pharma preclinical portfolio.
Innate Pharma is eligible for up to $855 million in opt-in payments, development and commercial milestones and high-single to double-digit tiered royalties on net sales for this molecule if the option is exercised prior to the molecule reaching clinical development. After opt-in and up to the start of a Phase III clinical trial, AstraZeneca will incur all the development costs. Innate retains the right to participate in cost sharing for Phase III clinical trials in order to receive 50% profit and loss sharing within the EU.
Laurent Gauthier et al, 2019. Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity Cell Mittal et al, 2018. Overcoming Acquired PD-1/PD-L1 Resistance with CD38 Blockade Cancer Discov. Cerwenka et al, 2018. Natural killers join the fight against cancer Science Chiossone et al, 2018. Natural killer cells and other innate lymphoid cells in cancer Nat Rev Immunol. Mamessier et al, 2011. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity The Journal of clinical investigation Bryceson et al, 2009. Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors Blood