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Two posters presented by Bristol-Myers Squibb and Innate Pharma
Innate Pharma SA (the “Company” - Euronext Paris: FR0010331421 – IPH), the innate immunity company developing first-in-class therapeutic antibodies for cancer and inflammatory diseases, announces today that new preclinical data on lirilumab, a first-in-class KIR checkpoint inhibitor, in combination with elotuzumab were presented today at the 56th ASH Annual Meeting in San Francisco, CA.
Elotuzumab is an antibody targeting CS1 (signaling lymphocyte activation molecule family member 7, or SLAMF7), a glycoprotein expressed on the surface of multiple myeloma (MM) tumor cells. Elotuzumab can recruit and trigger natural killer (NK) cells to kill MM tumor cells, through a process called antibody-dependent cellular cytotoxicity (ADCC). This ADCC process is negatively regulated by KIR inhibitory receptors on NK cells. Thus, combination treatment with lirilumab, an anti-KIR antibody, and elotuzumab has strong scientific rationale. The two posters presented show that lirilumab enhances elotuzumab activity in vitro and in vivo and support the rationale for the ongoing Phase I clinical trial combining these agents in MM.
“Lirilumab Enhances Anti-Tumor Efficacy of Elotuzumab”
In an in vitro model of two MM cell lines, activation of peripheral blood NK cells from healthy donors was significantly enhanced, in a dose-dependent manner, by both lirilumab and elotuzumab independently and further enhanced by the combination of both antibodies. The best combinatorial effect was observed in response to MM cells expressing low densities of CS1. These data suggest that lirilumab treatment may increase the therapeutic efficacy of elotuzumab.
In double-transgenic mice engrafted with human MM tumor cells and treated when high tumor volumes were reached, combination treatment with lirilumab and elotuzumab resulted in a significantly stronger anti-tumor effect and increased survival of the mice, when compared to either antibody treatment alone.
In conclusion, blockade of KIR with lirilumab was able to augment elotuzumab mediated ADCC in vitro and synergized with elotuzumab to mediate potent anti-MM activity in vivo.
“Effects of IL-21, KIR Blockade, and CD137 Agonism on the Non-Clinical Activity of Elotuzumab”
IL-21 , agonist CD137 mAb and lirilumab were examined for their ability to augment elotuzumab activity in vitro and in vivo mouse models. Although IL-21 was able to increase elotuzumab mediated ADCC in vitro it showed little or no enhancement of elotuzumab activity in a xenograft tumor model. CD137 agonism showed minimal enhancement of elotuzumab ADCC in vitro but was able to synergize with elotuzumab in vivo to mediate potent anti-tumor activity in a xenograft tumor model. Blocking the inhibitory KIR pathway with lirilumab was able to augment elotuzumab mediated ADCC in vitro and synergized with elotuzumab in vivo, mediating potent anti-tumor activity in a KIR2DL3 transgenic and RAG deficient mouse model.