학술논문
Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy
Document Type
Article
Author
Okaji, Yurai; Tsuno, Nelson H.; Tanaka, Minoru; Yoneyama, Satomi; Matsuhashi, Mika; Kitayama, Joji; Saito, Shinsuke; Nagura, Yutaka; Tsuchiya, Takeshi; Yamada, Jun; Tanaka, Junichiro; Yoshikawa, Naoyuki; Nishikawa, Takeshi; Shuno, Yasutaka; Todo, Tomoki; Saito, Nobuhito; Takahashi, Koki; Nagawa, Hirokazu
Source
Subject
*TUMORS
*CANCER treatment
*COLON cancer
*IMMUNOGLOBULINS
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Language
ISSN
0959-8049
Abstract
Abstract: 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. [Copyright &y& Elsevier]