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Researchers unveil strategy for creating actively-programmed anti-cancer molecules

all synthetic molecules and a well-known catalytic monoclonal antibody, mAb38C2, through chemical bonding, a modification that resulted in the reprogramming of the specificity of the antibody to match the binding specificity of the small molecule. In this way, the antibodies were directed to the target avb3 integrin-a cell membrane protein expressed on a variety of cancers and the vasculatures they produce.

"Key to this unique approach is the ability of the small molecule targeting agents-called programming agents or adapters-to selectively react in the antibody binding sites without compromising the targeting property of the adapters," notes Sinha.

The results showed those mice treated with the new compound developed significantly fewer metastases than those treated with other similar compounds or the antibody alone. These results, the study noted, were a "significant enhancement in the therapeutic efficacy" of the integrin antagonist directly attributable to the chemically programmed antibody approach.

Moreover, the study indicated that this approach allows for the effective assembly of chemically programmed antibodies in vivo or in vitro, widening the possibilities for their therapeutic application. The compound could be created in vitro and delivered as a conventional single therapy. Alternately, the small molecule and antibody could be injected separately, with the new complex formed in vivo. The authors note that even though the administration of two separate compounds might complicate regulatory approval, the regimen could have advantages-for example, an imaging agent could be attached to the small molecule, allowing a physician to monitor localization of a drug before arming the agent with the antibody molecule.


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Source:Scripps Research Institute


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