1. VEGF kinoid vaccine, a therapeutic approach against tumor angiogenesis and metastases
- Author
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Bernard Bizzini, Sébastien Paturance, Daniel Zagury, Robert C. Gallo, Farhad Haghighi Rad, Philippe Genne, Georges Uzan, Patrick Larcier, Hélène Le Buanec, Bernhard Ryffel, Armand Bensussan, Garcia, Marie, Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neovacs S.A [Paris], Oncodesign [Dijon], Institut Transgenose, Centre National de la Recherche Scientifique (CNRS), Différenciation, intéraction, activation et migration des sous-populations lymphocytaires humaines, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de médecine moléculaire (Im3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Human Virology (IHV), University of Maryland [Baltimore County] (UMBC), and University of Maryland System-University of Maryland System
- Subjects
Vascular Endothelial Growth Factor A ,Lung Neoplasms ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,MESH: HT29 Cells ,MESH: Cancer Vaccines ,Neovascularization ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Neoplasms ,Rhabdomyosarcoma ,MESH: Immune Sera ,MESH: Animals ,MESH: Neoplasms ,Neoplasm Metastasis ,[INFO.INFO-BT]Computer Science [cs]/Biotechnology ,Mice, Inbred BALB C ,0303 health sciences ,Multidisciplinary ,Neovascularization, Pathologic ,biology ,MESH: Antibody Formation ,3. Good health ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,030220 oncology & carcinogenesis ,MESH: Immunization ,Female ,medicine.symptom ,Growth inhibition ,Colorectal Neoplasms ,HT29 Cells ,medicine.drug ,MESH: Xenograft Model Antitumor Assays ,MESH: Cell Line, Tumor ,Paclitaxel ,Bevacizumab ,MESH: Mice, Inbred BALB C ,Mice, Nude ,Cancer Vaccines ,Antibodies ,03 medical and health sciences ,Immune system ,Cell Line, Tumor ,medicine ,MESH: Mice, Nude ,Animals ,Humans ,MESH: Paclitaxel ,MESH: Mice ,030304 developmental biology ,MESH: Humans ,business.industry ,Immune Sera ,MESH: Antibodies ,MESH: Rhabdomyosarcoma ,MESH: Vascular Endothelial Growth Factor A ,medicine.disease ,Xenograft Model Antitumor Assays ,MESH: Neoplasm Metastasis ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,MESH: Lung Neoplasms ,[INFO.INFO-BT] Computer Science [cs]/Biotechnology ,chemistry ,Antibody Formation ,Immunology ,Cancer research ,biology.protein ,Immunization ,business ,MESH: Neovascularization, Pathologic ,MESH: Female ,Keyhole limpet hemocyanin ,MESH: Colorectal Neoplasms - Abstract
International audience; Tumor growth depends on blood supply, requiring the development of new vessels, and vascular endothelial growth factor (VEGF) plays a central role in neoangiogenic processes. For this reason, VEGF represents a target for the development of new therapeutic antiangiogenic molecules. Clinical trials using anti-VEGF mAbs such as bevacizumab have validated the efficacy of this therapeutic approach but have also revealed adverse effects. Here we report that a VEGF-derived immunogen, consisting of a heterocomplex of a murine (m)VEGF and keyhole limpet hemocyanin, called "mVEGF kinoid," triggered a strong Ab immune response in mice. The anti-VEGF Abs inhibited both the proliferation of human umbilical vein endothelial cells cultured in the presence of mVEGF and the binding of mVEGF to its receptor-2 Flk-1. In mVEGF kinoid-immunized BALB/c mice challenged with syngeneic CT26 colorectal tumor cells, the number and size of lung metastases were significantly decreased. In human (h)VEGF kinoid-immunized BALB/c mice, high levels of serum Abs to hVEGF were present, and purified IgG from these mice decreased by > or =50% the tumor growth of human A673 rhabdomyosarcoma cells and HT29 colon carcinoma xenografted in Swiss nude and NOD/SCID mice, respectively. Tumor cell growth inhibition was similar to that observed in mice receiving therapeutic doses of bevacizumab. These experiments suggest that a therapeutic vaccine containing VEGF kinoid may represent a strategy for safely combating VEGF-dependent neovascularization and metastases occurring in malignant tumors.
- Published
- 2007
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