Oncomatryx has developed antibody-drug conjugates that target proteins located in the tumor microenvironment. A novel route to cancer treatment, directed not against tumor epithelial cells, but the stromal cancer-associated fibroblasts and endothelial cells that promote their invasiveness, immune suppression and drug resistance.
ONCOMATRYX ANTIBODY DRUG CONJUGATES
Antibody-drug conjugates comprise a recombinant human antibody, covalently bound, by means of synthetic linkers, to highly cytotoxic drugs. The main goal of this structure is to combine the pharmacological power of small cytotoxic drugs (300 to 1000 Da), with the high specificity of monoclonal antibodies aimed at tumor-associated antigens.
The antibody must show high affinity and specificity for a tumor-associated antigen, whose expression in normal cells must be restricted. The antibody must also be internalized rapidly and efficiently in target cells.
The cytotoxic agent has to be released only inside the target cells, once the ADC has been internalized. The most frequently used cytotoxic agents for ADCs are drugs that damage DNA, such as calicheamicins and duocarmycins, or drugs targeting microtubules, such as auristatins and maytansinoids.
Linkers that bind the cytotoxic agent to the antibody are designed to be stable in blood allowing a safe systemic administration, and cleavable within the target cells to release the cytotoxic agent.
The antibody-drug conjugates generated by Oncomatryx comprise human IgG1 antibodies, targeting cancer-associated fibroblasts and endothelial cells, conjugated to a 780 Da cytotoxic agent that inhibits tubulin polymerization and destabilizes microtubules.
Oncomatryx proprietary linkers enhance the antitumor efficacy of ADCs 1000 times compared to the classical linkers they are derived from.