Oncological and ophthalmological diseases are increasingly treated with antiangiogenic agents. These agents have different intensities and duration of effects that should be considered to choose the most suitable therapy. Our purpose was to evaluate the synergistic effect of two drugs, jointly administered as a pharmaceutical compound, in two animal models.
Corneal neovascularization was induced in three groups of nine white New Zealand rabbits, applying a filter paper disk soaked in 1 M NaOH on the central cornea (Ormerod et al., Invest Ophthalmol Vis Sci 30:2148–2153, 1989). Group one was treated immediately after injury with intravenous Suramab, compound of Bevacizumab + Suramin, and group two with intravenous Bevacizumab. A third group of non-treated rabbits was included as control group. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel index (NVI) was calculated using the Image J Program. Neovessels formation was quantified and given a score from 0 to 4 to each quadrant according to the centripetal growth of the longest vessel. Colorectal animal model: 6- to 8-week-old male BALB/c mice were inoculated with cancer cells. Seven days after tumor inoculation, four groups of BALB/c mice were treated with intravenous Bevacizumab (n = 9); intravenous Suramin (n = 10); intravenous Suramab (n = 10); and intravenous saline solution (n = 4). Tumor growth was assessed twice weekly by caliper measurement.
The NVI was remarkably inferior in the group of rabbits treated with intravenous Suramab compared with controls after 35 days of follow-up. A greater inhibitory effect was obtained with Suramab compared to that obtained with Bevacizumab. Suramab significantly reduced tumor volume and prolonged survival of mice compared to controls.
Suramab strongly reduced neovascularization in a rabbit model of corneal angiogenesis and induced a potent antitumoral effect in mice.
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We are grateful to Guillermo Gastón, Norma Montalbetti, and Soledad Arregui for their skillful technical assistance. This work was supported by a grant from Universidad Austral.
Conflict of interest
An international patent application has been submitted about Suramab (patent pending). Title of the patent: Synergistic pharmaceutical composition useful for inhibiting corneal and retinal neovascularization (angiogenesis), and in other organs, in a human being or animal. (10) Publication number: WO2009/022897;(21) Application Number: PCT/MX2008/000104;(51) International Patent Classification: A61 K 45/06 (2006.01); A61P 27/02 (2006.01); A61P 35/00 (2006.01) (71) Applicant(s): Asociación Civil De Estudios Superiores [AR/AR]; Av. Juan de Garay No. 125 Ciudad de Buenos Aires C1063ABB; (AR) (for all designated states except US) RIVAS CUEVAS, Claudio Manuel [MX/MX]; Ruiseñor No. 51-B Col. El Rosedal México, D.F.04330 (MX) (for all designated states except US)GALLO BARRACO, Juan Eduardo María [AR/AR]; Paraná 945, 3er Piso Ciudad de Buenos Aires C1017AAS (AR) (for US only).
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Lopez, E.S., Rizzo, M.M., Croxatto, J.O. et al. Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization. Cancer Chemother Pharmacol 67, 723–728 (2011). https://doi.org/10.1007/s00280-010-1457-z