Novel monoclonal antibody that enhances natural killer (NK) cell cytotoxicity against multiple myeloma (MM): Preclinical data and interim phase I clinical trial results
2016
3032 Background: MM is increasing in incidence and remains incurable. NK cells have modest killing activity against MM cells in part because of inhibitory signals from HLA class 1 antigens which act via the KIR receptors on NK cells. A novel anti-KIR
blocking antibody(1–7F9 named IPH 2101) enhances patient NK cell cytotoxicity against autologous MM tumor cells in vitro and appears safe in an ongoing phase 1 clinical trial. Methods: NK cells from healthy controls or patients were pre-treated with IPH 2101 or IgG4 isotype control and co-cultured with MM cell lines or autologous MM tumor targets. NK cell production of
interferon-gamma(IFN-γ) or
granzyme B(GrB) were measured by ELISPOT. An open-label, single-agent, phase 1 dose escalation study of IPH 2101 is being conducted in patients with relapsed/refractory MM. KIR binding, pharmacokinetics, pharmacodynamics, effects on NK cell maturation, and biological effects of IPH 2101 are being monitored in all patients. Results: At an effector to target (E:T) ra...
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