A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

Ryota Tamura, Masato Fujioka, Yukina Morimoto, Kentaro Ohara, Kenzo Kosugi, Yumiko Oishi, Mizuto Sato, Ryo Ueda, Hirokazu Fujiwara, Shinobu Noji, Naoki Oishi, Kaoru Ogawa, Yutaka Kawakami, Takayuki Ohira, Kazunari Yoshida, Masahiro Toda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number5758
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Neurofibromatosis 2
vaccines
Vascular Endothelial Growth Factor Receptor
Vaccines
Tumors
T-cells
tumors
lymphocytes
Neurilemmoma
Cytotoxic T-Lymphocytes
Subunit Vaccines
peptides
Vaccination
Audition
Surgery
Vascular Endothelial Growth Factor A
hearing
Tumor Burden
antibodies
surgery

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2. / Tamura, Ryota; Fujioka, Masato; Morimoto, Yukina; Ohara, Kentaro; Kosugi, Kenzo; Oishi, Yumiko; Sato, Mizuto; Ueda, Ryo; Fujiwara, Hirokazu; Noji, Shinobu; Oishi, Naoki; Ogawa, Kaoru; Kawakami, Yutaka; Ohira, Takayuki; Yoshida, Kazunari; Toda, Masahiro.

In: Nature communications, Vol. 10, No. 1, 5758, 01.12.2019.

Research output: Contribution to journalArticle

Tamura, Ryota ; Fujioka, Masato ; Morimoto, Yukina ; Ohara, Kentaro ; Kosugi, Kenzo ; Oishi, Yumiko ; Sato, Mizuto ; Ueda, Ryo ; Fujiwara, Hirokazu ; Noji, Shinobu ; Oishi, Naoki ; Ogawa, Kaoru ; Kawakami, Yutaka ; Ohira, Takayuki ; Yoshida, Kazunari ; Toda, Masahiro. / A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2. In: Nature communications. 2019 ; Vol. 10, No. 1.
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