Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy.
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 5x10(7) 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.
Department of Transfusion Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. okaji-tky@umin.ac.jp
Yurai
Y
Okaji
Nelson H
NH
Tsuno
Minoru
M
Tanaka
Satomi
S
Yoneyama
Mika
M
Matsuhashi
Joji
J
Kitayama
Shinsuke
S
Saito
Yutaka
Y
Nagura
Takeshi
T
Tsuchiya
Jun
J
Yamada
Junichiro
J
Tanaka
Naoyuki
N
Yoshikawa
Takeshi
T
Nishikawa
Yasutaka
Y
Shuno
Tomoki
T
Todo
Nobuhito
N
Saito
Koki
K
Takahashi
Hirokazu
H
Nagawa
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000098:blood supply / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014471:Umbilical Veins / Q000166:cytology / Q000276:immunology*
D019496:Cancer Vaccines; D007371:Interferon-gamma