MDP01: anti EGFR

Structure of MDP01

We produced a fully human version of a peptabody molecule, called MDP01, to target the Epidermal Growth Factor receptor EGFR. The mature MDP01 molecule consists of five identical 122 amino acid subunits made of three main domains (Figure 1A):

MDP01. A. Monomeric structure. B. Pentameric structure.

Concept of MDP01 Technology

We took advantage of the peptabody concept to target specifically cancer cells overexpressing EGFR. For efficient EGFR binding and subsequent activation of its cell signalling pathway, a high density of receptor molecules is required. This ensures an efficient targeting of cancer cells overexpressing EGFR and therefore limits effects on cells expressing normal physiological levels of the receptor.
MDP01-mediated receptor multimerization induces an aberrant cell signal leading to apoptosis of cancer cells (Figure 2, Fattah et al., 2005).

Targeting of EGFR overexpressing cancer cells with MDP01.

High Efficacy of MDP01 to disrupt tumors

MDP01 can disrupt a solid tumor within one hour by inducing apoptosis. This action is specific to tumors overexpressing EGF receptors (no apoptosis induction on normal cells).

MDP01. A. Cytotoxic effect on spheroid tumors (DU145 model)

References:
Fattah, O. M., Cloutier, S. M., Kundig, C., Felber, L. M., Gygi, C. M., Jichlinski, P., Leisinger, H. J., Gauthier, E. R., Mach, J. P., and Deperthes, D. (2005). Peptabody-EGF: a novel apoptosis inducer targeting ErbB1 receptor overexpressing cancer cells. Int J Cancer 2006.
Terskikh, A. V., Le Doussal, J. M., Crameri, R., Fisch, I., Mach, J. P., and Kajava, A. V. (1997). "Peptabody": a new type of high avidity binding protein. Proc Natl Acad Sci U S A 94, 1663-1668.