Inhibition of IGF1R with AVE1642: A Promising Approach for Targeted Cancer Therapy

The IGF1R plays a crucial role in the proliferation and survival of numerous cancer cells, making it a promising target for cancer therapy. The antibodies EM164 and its humanized counterpart AVE1642 have been developed to specifically target the human IGF1R with high affinity, blocking IGF-1 binding and receptor activation, and thereby inhibiting cell growth and survival. These antibodies demonstrate similar IGF-1R affinity and biological activity without binding to the closely related insulin receptor, reducing the risk of metabolic side effects.

In vitro, EM164 significantly inhibited the growth of select tumor cell lines, including colon, pediatric neuroblastoma, sarcoma, and NSCLC. In an in vivo IGF1R-dependent tumor model using mice, EM164 showed dose-dependent anti-tumor activity, with complete regressions observed at the highest dose. EM164 also exhibited anti-tumor effects in a human pancreatic cancer model and reduced the growth of liver metastases in a tumor metastasis model.

Treatment with EM164 resulted in a significant decrease in IGF1R protein levels in all tested tumor xenografts, both responsive and non-responsive to the therapy. These findings indicate that EM164, by downregulating the IGF1R receptor, effectively inhibits tumor growth. The development of AVE1642 is supported for the treatment of cancer, although the responsiveness of tumors to this antibody treatment varies, underscoring the importance of understanding tumor characteristics that influence treatment susceptibility.