On April 18, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported a new set of preclinical data further validating the potential of its first-in-class anti-MICA/B antibody IPH4301 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana, USA (Press release, Innate Pharma, APR 18, 2016, View Source [SID:1234511087]).
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Poster #1491 reports that IPH4301, a humanized antibody, binds with high affinity to MICA/B and is a potent cytotoxic antibody, inducing direct tumor cell killing by ADCC. Moreover, an additional mode-of-action of the same antibody was revealed, whereby the antibody has the potential to overcome immunosuppression in tumors.
Among the highly immune-suppressive cell types in cancer are tumor-associated macrophages or myeloid-derived suppressor cells (MDSC), which can reduce NK and T cell activities. In vitro, IPH4301 could overcome immunosuppression by macrophages, restoring NK cell antibody-mediated killing to levels seen in the absence of suppressor macrophages. In addition, IPH4301 blocked MICA/B-induced down-modulation of NKG2D receptors on NK and CD8 T cells, thus disrupting a second immuno-suppressive mechanism. Finally, treatment with IPH4301 restored NK cell infiltration, prevented tumor growth and improved survival in different in vivo tumor models.
Nicolai Wagtmann, CSO of Innate Pharma, said: "We are enthusiastic about IPH4301 as a therapeutic candidate because of its dual mode of action, combining potent ADCC-mediated tumor killing with interesting immuno-modulating properties. The ability of IPH4301 to interfere with these immune-suppressive pathways, while at the same time retaining high direct ADCC potency, makes for a novel, unique proposition in the immune-oncology landscape. IND-enabling studies will start in 2016".