Chemical Adaptor Immunotherapy: Design, Synthesis, and Evaluation of Novel Integrin-Targeting Devices

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Abstract
A series of β-diketone derivatives of RGD peptidomimetics that selectively bind to αvβ3 and αvβ5 integrins were synthesized and covalently docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The resulting targeting devices strongly and selectively bound to human cancer cells expressing integrins αvβ3 and αvβ5 as analyzed by flow cytometry. In vitro and in vivo studies revealed that these novel integrin-targeting devices efficiently inhibit tumor growth. Thus, the combination of β-diketone derivatives of RGD peptidomimetics that target cell surface integrins αvβ3 and αvβ5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.