Combination immunostimulatory agents with cytotoxic drugs are emerging as a promising approach for potentially curative tumor therapies. However, advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies. These trials generally show suboptimal efficacy.

In the OnlineFirst September 9, 2014 edition of Molecular Cancer Therapeutics (to be published in print on November 13, 2014) Thomas List and Dario Neri at the Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Zurich, Switzerland, and Giulio Casi from Philochem AG, Otelfingen, Switzerland, for the first time describe a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. [1]

They describe that in particular Interleukin 2 (IL-2; Aldesleukin/Proleukin®; Prometheus Laboratories), a type of cytokine signaling molecule in the immune system, and the disulfide-linked maytansinoid DM1 a potent microtubule-targeted compound that inhibit proliferation of cells at mitosis, could be coupled to the F8 antibody, and in a site-specific manner, be directed against the alternatively spliced EDA domain of fibronectin. As tested in two different immunocompetent mouse models, this may yield a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo.

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