Abstract 3830: Monoclonal and bispecific antibodies against human insulin-like growth factors in oncology

Abstract

Abstract The insulin-like growth factor (IGF) axis plays an important role in cell growth and differentiation. During the past decade, IGF type 1 receptor (IGF-1R) was deemed a promising target for cancer therapy. The major challenge is that abnormal activation of IGF-1R ligands (IGF-I and IGF-II) exists in series of cancers and contributes to the resistance in IGF-1R-targeted therapies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Up to date, we have developed different antibody formats against IGF-II or IGF-I/II, including one fully human IgG m708.5 with picomolar affinity[1], two bispecific antibodies (BsAbs) m660 [2, 3] and m67 [4], and one small-size nanobody s7g1 (15 kDa) (unpublished data). BsAb m67 has exhibited in cynomolgus macaques and high stability in serum. Compared with large-size antibodies, nanobody s7g1 has distinct advantages because of greater and more rapid tissue accumulation. All antibodies can eliminate the efflux of IGFs from tumor tissues and circulating IGFs in the serum. The m708.5 shows dual-specific for IGF-I/IGF-II with the highest affinities. The m708.5 has shown satisfying preclinical activities against a broad spectrum of human cell lines. When tested in neuroblastoma cell lines, m708.5 showed strong antitumor activity alone and in combination with chemotherapeutic agents [5]. Therefore, the anti-IGF-I/II antibodies offers an alternative approach to target both the IGF-1R and IR-A signaling pathways through the inhibition of IGF-I/II. These results support the clinical development of anti-IGF antibodies for solid tumors with potential for synergy with chemotherapy. Acknowledgements: This work was supported by the Science and Technology Development Fund of Macau (FDCT/131/2016/A3).