A series of -diketone derivatives of RGD peptidomimetics that selectively bind to Rv 3 and Rv 5 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 Rv 3 and Rv 5 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 -diketone derivatives of RGD peptidomimetics that target cell surface integrins Rv 3 and Rv 5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.

Background:The class IA PI3K isoform p110␣ is a promising drug target in cancer therapy yet its role in lymphocytes is not known. Results: Lymphocyte function was minimally affected by p110␣ inhibition both in vitro and in vivo. Conclusion: Selective inhibition of p110␣ preserves lymphocyte function. Significance: The study raises confidence that selective p110␣ inhibitors in cancer therapy will not be immunosuppressive.

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