A Phase II study of Viagenpumatucel-l (HS-110) in combination with low-dose Cyclophosphamide versus physician's choice in patients with advanced non-small cell lung cancer

Background Viagenpumatucel-L (HS-110) is an allogeneic cell-based therapeutic cancer vaccine for the treatment of advanced NSCLC. The vaccine is composed of a cell line expressing a defined repertoire of tumor antigens (MAGE-A3, NY-ESO-1, LAGE-1, and others) that are chaperoned by a modified, secretable, heat shock protein (gp96-Ig) with dual antigen binding and adjuvant activity. Importantly, gp96-Ig delivers these cell-derived antigens directly to a patient’s own antigen presenting cells and shuttles those antigens to MHC-I via the cross-presentation pathway. This preferential trafficking to MHC-I leads to exclusive activation of CD8+ cytotoxic T cells. In addition, the specific delivery of cell-derived antigens by gp96-Ig enables vaccination across MHC barriers and leads to potent CD8+ T cell activation in response to physiologic antigen concentrations (femto-molar). These elements are believed to provide several advantages over previous peptide vaccines by providing an opportunity for protection against a broad spectrum of tumor antigens and therefore addressing the underlying genetic/antigenic heterogeneity of NSCLC within individual tumors. In addition, delivery of antigens to MHC-I and activation of CD8+ cells is proposed to provide a unique advantage compared to other cell-based vaccines, wherein antigens are preferentially processed through the exogenous pathway and displayed on MHC-II.