Monoclonal antibodies (mAbs), either mono-or bispecific (bsAb), represent one of the most successful approaches to treat many types of malignancies. However, there are certain limitations to the use of full length mAbs for clinical applications, which can be overcome by engineered antibody fragments. The aim of the present study was to develop a small bsAb, in the format of a single-chain diabody (scDb), to efficiently target two proteins, the hERG1 potassium channel and the 1 subunit of integrin receptors, which specifically form a macromolecular complex in cancer cells.We provide evidence that the scDb we produced binds to the hERG1/1 complex in cancer cells and tissues, whereas does not bind to the hERG1 channel in non-pathological tissues, in particular the heart. The scDb-hERG1-1 (1) downregulates the formation of the hERG1/1 complex, (2) inhibits Akt phosphorylation and HIF-1 expression and (3) decreases cell survival, proliferation and migration in vitro. These effects only occur in cancer cells (either colon, pancreatic or breast), but not in normal cells. In vivo, the scDb-hERG1-1 shows a good pharmacokinetic profile, with a half-life of 13.5 hours and no general, cardiac or renal toxicity when injected intravenously up to the dose of 8 mg/Kg. The scDb-hERG1-1 accumulates into subcutaneous xenografted tumors, arising from either colon or pancreatic human cancer cells, and induces a reduction of tumor growth and vascularization.Overall, the scDb-hERG1-1 represents an innovative single-chain bispecific antibody for therapeutic applications in solid cancers which over express the hERG1/1 integrin signaling complex.

A theoretical model of the polarization properties of a 'Zeiss-type' coelostat is presented and discussed in detail. The Muller matrix describing the modification of the Stokes vector of the incident radiation as a result of the multiple reflections on the coelostat mirrors is derived as a function of the solar coordinates, the geometrical configuration of the coelostat, and the parameters defining the optical properties of the mirrors. These parameters, or more particularly, the index of refraction n and the extinction coefficient k, have been evaluated by means of laboratory measurements performed on a series of specimens having characteristics similar to those of the coelostat mirrors. The geometry of the coelostat configuration is described in full detail. The theoretical model has been then particularized to the case of the Donati Solar Tower in Arcetri, and some experimental measurements have been performed to check the correctness of the mode1. These measurements show the basic adequacy of the mathematical model, although some offset terms are found in the Stokes parameters U and V.

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