The road towards vaccine that prevent tumor formation


Federica Cavallo

At present Federica Cavallo’s lab is combining immune regulators of various kind and gene-based vaccines to prevent and cure autochthonous cancers in pre-clinical models (transplantable tumors, mice transgenic for oncogenes, naturally occurring cancers in dogs). Many pre-clinical data have been collected demonstrating the effectiveness of anti-ErbB2 vaccination (Quaglino et al., Cancer Res 2004; Quaglino et al., J Clin Invest 2004; Quaglino et al., Vaccine 2005; Quaglino et al., Cancer Res 2010; Quaglino et al. Cancers 2011) or vaccination against Angiomotin, an antigen express by the tumor vasculature (Holmgren et al., PNAS 2006; Arigoni et al., Angiogenesis 2012). More recently, xenogeneic DNA vaccination against CSPG4, a molecule highly expressed by human and canine malignant melanoma has been successfully tested in client-owned dogs with surgically resected oral malignant melanoma. The overall survival in vaccinated as compared to non-vaccinated dogs was significantly extended, suggesting that CSPG4 vaccination is effective for the treatment of malignant melanoma(Mayayo et al., Vet J 2011; Cavallo et al., Expert Opin Biol Ther 2014; Riccardo et al., Clin Cancer Res 2014).

Identification of cancer biomarkers and oncoantigens (Lollini et al., Nat Rev Cancer 2006; Bolli et al., Am J Cancer Res 2011; Cavallo et al., Cancer Immunol Immunother 2011; Iezzi et al., OncoImmunol 2012), i.e. a class of persistent tumor antigens not prone to escape from immune recognition, expressed either by tumor cells or by cells in the tumor microenvironment, is another central objective of the lab. A major effort is devoted to grab new knowledge on tumor and microenvironment transcriptome from microarray analysis and next generation sequencing data (Astolfi et al., Cancer Immunol Immunother 2005; Calogero et al., Breast Cancer Res 2007; Cavallo et al., Nat Rev Cancer 2007; Calogero et al., Cancer Immunol Immunother 2008; Bolli et al., Am J Cancer Res 2011). These technologies are currently exploited to tease apart new mechanisms of carcinogenesis inhibition and to spot both miRNA and new oncoantigens expressed by cancer stem cells to be exploited in a new generation of antitumor treatments (Arigoni et al., Am J Pathol 2013; Riccardo et al., Bmc Genomics 2014; Spadaro et al., FASEB J 2014). This approach led us to the identification of the noninflammatory role of high mobility group box 1/toll-like receptor 2 axis in the self-renewal of mammary cancer stem cells (Conti et al., FASEB J 2013). The role of TLR2 in carcinogenesis is still object of active research in the lab. Other cell membrane molecule - including TMPRSS4 - with high expression on cancer stem cells, but restricted distribution on normal tissue, have been identified with a similar approach and are now under investigation as vaccination targets.

Finally, the role of immunosurveillance in sculpting an incipient cancer cell population and its consequences on the immunogenicity of the developing tumor are active fields of investigation in the lab (Bandini et al., OncoImmunol 2013; Macagno et al., J Immunol 2014). The molecules that are recognized by this spontaneous immune response might represent ideal target antigens for preventive anti-tumor vaccination.

Unit Members