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, Tetsuro Hikichi, Shinobu Noji, Naoki Oishi, Kaoru Ogawa, Yutaka Kawakami, Takayuki Ohira, Kazunari Yoshida and Masahiro Toda ()
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Ryota Tamura: Keio University School of Medicine
Masato Fujioka: Keio University School of Medicine
Yukina Morimoto: Keio University School of Medicine
Kentaro Ohara: Keio University School of Medicine
Kenzo Kosugi: Keio University School of Medicine
Yumiko Oishi: Keio University School of Medicine
Mizuto Sato: Keio University School of Medicine
Ryo Ueda: Keio University School of Medicine
Hirokazu Fujiwara: Keio University School of Medicine
Tetsuro Hikichi: OncoTherapy Science, Inc.
Shinobu Noji: Keio University School of Medicine
Naoki Oishi: Keio University School of Medicine
Kaoru Ogawa: Keio University School of Medicine
Yutaka Kawakami: Keio University School of Medicine
Takayuki Ohira: Keio University School of Medicine
Kazunari Yoshida: Keio University School of Medicine
Masahiro Toda: Keio University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13640-1

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