TY - JOUR
T1 - A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2
AU - Tamura, Ryota
AU - Fujioka, Masato
AU - Morimoto, Yukina
AU - Ohara, Kentaro
AU - Kosugi, Kenzo
AU - Oishi, Yumiko
AU - Sato, Mizuto
AU - Ueda, Ryo
AU - Fujiwara, Hirokazu
AU - Noji, Shinobu
AU - Oishi, Naoki
AU - Ogawa, Kaoru
AU - Kawakami, Yutaka
AU - Ohira, Takayuki
AU - Yoshida, Kazunari
AU - Toda, Masahiro
N1 - Funding Information:
The authors thank Ms. Yukiko Matsushima and Mr. Kazuto Hagimura of the Keio University Hospital Clinical and Translational Research Center (CTR) for monitoring, Mr. Ryo Takemura and Mr. Ryota Ishii of the Keio University Hospital CTR for assistance with statistical analysis, and Ms. Naoko Tsuzaki of the Department of Neurosurgery for technical assistance with laboratory procedures. We also thank Ms. Akemi Hori, Ms. Emiko Seki, Ms. Kaori Kaseda, and Ms. Kana Watanabe of the Department of Otorhinolaryngology for performing the hearing examinations. We thank Dr. Owen Proudfoot of the Edanz Group (www.edanzediting.com/ac) for editing a draft of this paper. This work was supported in part by grants from the Japan Society for the Promotion of Science (JSPS) (17H04306 to M.T., 18K08951 to R.U.), and by the Japan Agency for Medical Research and Development (19lm0203088h0001 to M.T.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The anti-VEGF antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Theoretically, vascular endothelial growth factor receptors (VEGFRs)-specific cytotoxic T lymphocytes (CTLs) can kill both tumor vessel cells and tumor cells expressing VEGFRs. Here we show an exploratory clinical study of VEGFRs peptide vaccine in seven patients with progressive NF2-derived schwannomas. Hearing improves in 2/5 assessable patients (40%) as determined by international guidelines, with increases in word recognition scores. Tumor volume reductions of ≥20% are observed in two patients, including one in which bevacizumab had not been effective. There are no severe adverse events related to the vaccine. Both VEGFR1-specific and VEGFR2-specific CTLs are induced in six patients. Surgery is performed after vaccination in two patients, and significant reductions in the expression of VEGFRs in schwannomas are observed. Therefore, this clinical immunotherapy study demonstrates the safety and preliminary efficacy of VEGFRs peptide vaccination in patients with NF2.
AB - The anti-VEGF antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Theoretically, vascular endothelial growth factor receptors (VEGFRs)-specific cytotoxic T lymphocytes (CTLs) can kill both tumor vessel cells and tumor cells expressing VEGFRs. Here we show an exploratory clinical study of VEGFRs peptide vaccine in seven patients with progressive NF2-derived schwannomas. Hearing improves in 2/5 assessable patients (40%) as determined by international guidelines, with increases in word recognition scores. Tumor volume reductions of ≥20% are observed in two patients, including one in which bevacizumab had not been effective. There are no severe adverse events related to the vaccine. Both VEGFR1-specific and VEGFR2-specific CTLs are induced in six patients. Surgery is performed after vaccination in two patients, and significant reductions in the expression of VEGFRs in schwannomas are observed. Therefore, this clinical immunotherapy study demonstrates the safety and preliminary efficacy of VEGFRs peptide vaccination in patients with NF2.
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U2 - 10.1038/s41467-019-13640-1
DO - 10.1038/s41467-019-13640-1
M3 - Article
C2 - 31848332
AN - SCOPUS:85076624326
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5758
ER -
