Minimally Toxic Prodrugs

Concerning the minimally toxic prodrug project, CoBioRes’ scientists are developing optimized chemotherapy treatments that are aimed at reducing systemic toxicity while preserving high antitumor efficacy.

Our core research and development interests include technologies that enable selective drug delivery to tumor tissues in order to improve the therapeutic index. Therefore, we are focusing on less toxic prodrug forms of existing chemotherapeutics that can be selectively activated in the tumor environment.

CoBioRes’ drug pipeline encompasses tetrapeptide-based chemotherapeutic agents, on the basis of their stability in human whole blood and for their selective reactivation by tumor microenvironment enzymes CD10, THOP1, DPP4 and FAP alpha.

Those agents meet 2 criteria:

  • They are pharmacologically inactive towards healthy tissue as a result of their inability to access the intracellular compartments of normal cells.
  • They are converted into an active cytotoxic agent at the tumor site only.

Prevention of intracellular uptake in the healthy tissues is achieved by conjugating the cytotoxic drug to a non-cell penetrating, blood-stable peptide. Conversion to the active agent is mediated by the cleavage of the peptide chain by extracellular peptidases found specifically in tumors. Indeed, a number of peptidases are overexpressed and oversecreted by tumor cells, tumor stromal cells or endothelial cells involved in tumor immunology and neoangiogenesis.

This approach can create a chemotherapy platform, where targeted delivery of approved chemotherapeutic drugs to cancer cells leads to a decrease in the systemic toxicity that is inherent to these chemotherapeutics.