Developing tumors initiate the formation of new vasculature, a process that is called angiogenesis. Until to date, angiostatic and vascular targeting approaches have only shown limited clinical success, most likely because the therapies were aimed at pathways that are not specific to the tumor or induce drug resistance.
The innovative approach of the Angiogenesis Laboratory is based on development of (multi-targeted) immunotherapies against cancer directly targeting the earliest markers of angiogenesis. This approach is expected to outperform other strategies, as (i) it is expected not to induce drug resistance and (ii) targeting early markers of angiogenesis provides a broad therapeutic opportunity in different cancers and in different stages of disease. This approach is expected to be a superior therapeutic approach against cancer.
It was shown by Huijbers et al. that vaccination against the extra-domain B containing form of fibronectin, a marker of the tumor vasculature, is an efficient strategy against cancer (Huijbers et al. FASEB J, 2010). We have now developed an effective strategy to break immune tolerance against self-antigens, called Immuno-BOOST (iBOOST). This strategy allows the induction of antibody responses against every self-antigen that serves as a target of disease (Huijbers et al. Vaccine, 2018). We have identified a series of hyper-specific targets that mark the tumor vasculature. Vaccines directed to these targets are in different stages of development.
Figure: The principle of breaking immunetolerance against self-antigens by iBOOST.