Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in...

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• OTS11101 is a novel peptide vaccine designed to inhibit angiogenesis.
• It functions by inducing cytotoxic T lymphocyte (CTL) cells targeting vascular endothelial cells expressing vascular endothelial growth factor (VEGF) receptor 1.

Purpose of the Study:

• To evaluate the safety, tolerability, maximum tolerated dose (MTD), and pharmacodynamic biomarkers of OTS11101 in patients with advanced solid tumors.
• To assess the vaccine's biological activity and potential as an anti-angiogenesis therapy.

Main Methods:

• A phase I clinical trial involving nine patients with advanced solid tumors.
• Patients received OTS11101 subcutaneously at doses of 1.0, 2.0, or 3.0 mg weekly for 28-day cycles.
• Safety assessments, pharmacodynamic biomarker analysis (CTL induction, VEGF receptors, gene expression via microarray) were performed.

Main Results:

• OTS11101 was generally well tolerated up to 3.0 mg weekly.
• The most frequent adverse events were grade 1 injection site reactions; grade 2 proteinuria and hypertension occurred in one patient each.
• Specific CTL induction was observed at 2.0 and 3.0 mg doses.
• Serum levels of soluble VEGF receptors 1 and 2 increased significantly post-vaccination.
• Gene expression analysis suggested T cell activation.

Conclusions:

• OTS11101 is well tolerated at doses up to 3.0 mg weekly in patients with advanced solid tumors.
• The vaccine demonstrates biological activity, evidenced by CTL induction and modulation of VEGF-related biomarkers.
• These findings support further investigation of OTS11101 as an anti-angiogenesis therapeutic.