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Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy

Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy,10.

Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy   (Citations: 10)
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Yurai Okaji, Nelson H. Tsuno, Minoru Tanaka, Satomi Yoneyama, Mika Matsuhashi, Joji Kitayama, Shinsuke Saito, Yutaka Nagura, Takeshi Tsuchiya, Jun Yamada, Junichiro Tanaka, Naoyuki Yoshikawahttp://academic.research.microsoft.com/io.ashx?type=5&id=31385669&selfId1=0&selfId2=0&maxNumber=12&query=
Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5×107 HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs’ membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. Our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer.
Journal: European Journal of Cancer - EUR J CANCER , vol. 44, no. 3, pp. 383-390, 2008
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