Pepscan’s VEGF targetted vaccine study published in PNAS
Researchers of Pepscan have developed a peptide-based vaccine enabling a successful active anti-tumor immunization therapy targeting the growth hormone Vascular Endothelial Growth Factor (VEGF). The encouraging preclinical results have just been published in the reputable international journal PNAS (Proceedings of the National Academy of Sciences).
VEGF is the pivotal growth factor for the formation of new blood vessels (angiogenesis). Targeting VEGF is a well established strategy to treat cancer, as demonstrated by the use of the monoclonal antibody bevacuzimab (Avastin®) which results in improved survival in patients with several types of cancer. To improve this strategy via a ployclonal approach, a team of Pepscan researchers developed a vaccine targetting VEGF via immunization with a 3D-structured peptide that mimics the bevacuzimab binding site.
The team designed and synthesized a truncated hVEGF-derived peptide (VEGF26-104), which contains an intact cys-knot fold of 3 SS-bonds. Binding and competition studies revealed that this peptide perfectly mimics the complete bevacuzimab binding site. The peptide adopts a clear secondary, native-like structure, including the typical cys-knot fold of VEGF. The study showed that the antigen’s correct 3-D structure is essential for achieving the desired neutralizing antibody response.
Subsequent studies in passive and active immunization animal models showed that vaccination with the peptide resulted in potent in vitro and in vivo VEGF-neutralizing activities. This novel VEGF vaccination strategy has the potential to outperform current clinical anti-VEGF treatment strategies. The vaccine has been partnered with the startup company Immunovo and is currently studied in a combined Phase-I/IIa clinical trial at the VU medical center in Amsterdam.
Ref: Wentink et al: Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity. Published on-line before print, October 17, 2016, doi: 10.1073/pnas.1610258113