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.
Highlights
Treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has reportedly resulted in tumor control and hearing improvement in Neurofibromatosis type 2 (NF2) patients[6], presumably because VEGF-A is essential for the growth of these tumors
Because schwannoma growth mainly depends on the VEGF-A/ VEGF receptor (VEGFR) pathway[12], bevacizumab has demonstrated therapeutic efficacy in NF2 patients
A review of the literature suggests that schwannoma shrinkage and hearing improvement occur in >50% of progressive NF2 patients treated with bevacizumab[6,13,14,15,16,17,18,19,20]
Summary
Treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has reportedly resulted in tumor control and hearing improvement in NF2 patients[6], presumably because VEGF-A is essential for the growth of these tumors. Some aspects of bevacizumab treatment are problematic, such as the need for frequent parenteral administration, side effects, apparent drug resistance, and rebound tumor progression after cessation[7]. We recently reported a pilot clinical study investigating VEGF receptor (VEGFR)[1] and VEGFR2 peptide vaccination in malignant glioma patients, in which the treatment exhibited safety, and yielded therapeutic effects in some patients[8]. We demonstrate VEGFRs expression in endothelial cells and tumor cells in NF2 schwannomas, and conduct an exploratory clinical investigation of VEGFRs peptide vaccination in patients with progressive NF2. Immunotherapy using VEGFRs peptides is safe and exhibits preliminary efficacy for NF2 patients. The efficacy of peptide vaccination alone for malignant diseases has far proved to be limited, it may have the capacity to slow the growth of benign tumors, including those in NF2 patients
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