Biological treatment for pancreatic cancer (Yeda)
Although early programs targeting MMPs (matrix metalloproteins) were largely unsuccessful due to adverse side effects, they remain a viable and highly desirable therapeutic target. The main obstacle in the attempts to target MMPs is the ability to selectively target individual family members. The present invention provides highly selective targeted therapy against MMP-7, which is strongly associated with aspects of cancer development such as angiogenesis and metastasis.
The innovative concept leading to this high selectivity is immunization with both a synthetic metal-protein mimicry molecule, previously developed by the present inventors, followed by the metalloenzyme itself (e.g. MMP-7). The resulting antibody exhibits exceptional degree of specificity towards MMP-7 over other MMPs.
The present technology offers an opportunity to re-introduce improved MMP-targeting agents to the cancer therapeutics market, in particular aggressive cancers that face a major unmet medical need. The present technology is based on a previous invention that was developed in Prof. Sagi's lab, of synthetic metal-protein mimicry molecules that mimic the conserved structure of the metalloenzyme catalytic zinc-histidine complex within the active site of each MMP enzyme.
These molecules were shown to be powerful immunogens in the generation of highly selective MMP antibodies since they recognize both electrical and structural determinants residing within the enzyme active site. The potential of this method to successfully generate MMP-targeting therapeutics was shown for MMP-9/2 inhibitory antibodies in mouse models of inflammatory bowel disease.
Prof Sagi and her team now take this invention a step further to achieve even higher specificity. They show that immunizing with the mimicking molecules described above, followed by immunization with the metalloenzyme itself increases selectivity further.
Implemented for MMP-7-targeting, this approach yielded an antibody with a 5 fold lower Ki towards MMP-7 than towards other MMPs (e.g. MMp-2 and MMP-9).
Highly selective
Safe avoids adverse effects that are associated with broad spectrum MMP inhibitors.
Efficient targeting a physiological active conformation of the enzyme
Therapy for MMP-7 associated diseases
Diagnostic tool for MMP-7 associated diseases
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