A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2.

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.

• Authors: 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, Masahiro Toda
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 5758 (12 17 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31848332 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Vaccines, Subunit
• Bevacizumab
• FLT1 protein, human
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adolescent
• Adult
• Bevacizumab (therapeutic use)
• Brain (diagnostic imaging, pathology, surgery)
• Brain Neoplasms (immunology, pathology, therapy)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Combined Modality Therapy (adverse effects, methods)
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Neurofibromatosis 2 (immunology, pathology, therapy)
• Radiosurgery
• Tomography, X-Ray Computed
• Treatment Outcome
• Tumor Burden (immunology)
• Vaccination (adverse effects, methods)
• Vaccines, Subunit (administration & dosage, adverse effects, immunology)
• Vascular Endothelial Growth Factor Receptor-1 (immunology, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (immunology, metabolism)
• Young Adult