Fully Human FAbs to IGF-1 and IGF-2

Insulin-like growth factors (IGF) IGF-1 and IGF-2 are polypeptides that play a role in important physiologic and pathologic processes including cell proliferation, survival, and migration. Overexpression of IGF-1 and IGF-2 is associated with poor prognosis for many cancers; increased serum level of IGF-2 especially is linked to a higher risk for colorectal, breast, prostate, and lung cancer. These associations make them promising targets for anticancer therapy. However, while a number of monoclonal antibodies targeting IGF1R, the receptor for IGF-1 and IGF-2, have been developed and shown to inhibit cancer cell growth, none have shown any significant benefit in clinical trials.  

Description

Pitt researchers have identified and characterized three fully human antigen binding fragments (Fabs) against IGF-1 and IGF-2 from a Fab phage display library. These binders showed very high binding affinity to both IGF-1 and IGF-2, as well as minimal aggregation as measured by dynamic light scattering. When used to treat a cancer cell-line that uses IGF-1R signaling for cell proliferation these Fabs reduced the phosphorylation level of IGF-1R in presence of IGF-1. These Fabs and their derivatives have the potential to be developed further into valuable therapeutics for cancer treatment by preventing binding of IGF-1 and IGF-2 to IGF-1R, thus blocking IGF-related signaling. In addition, multiple co-treatment strategies exist, which combine IGF-1 and IGF-2 blockades with existing drugs, that can be applied to fulfill unmet medical needs.

Applications

- Developing anticancer therapeutics

Advantages

- Neutralize IGF-1 and IGF-2 ligands directly, instead of targeting their receptor, IGF-1R
- Co-target IGF-1 and IGF-2, which could prevent the development of resistance to targeted cancer therapy
- High affinity for IGF-1 and IGF-2 makes these Fabs highly effective
- Fully human MAbs with minimum immunogeneticity concerns

Invention Readiness

In vitro

Related Publication(s)

Chen, Z., Liu, J., Chu, D., Shan, Y., Ma, G., Zhang, H., Zhang, X. D., Wang, P., Chen, Q., Deng, C., Chen, W., Dimitrov, D. S., & Zhao, Q. (2018). A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells. International Journal of Biological Sciences, 14(7), 799–806. https://doi.org/10.7150/ijbs.25928