OncoMed Pharmaceuticals, Inc., reported that anti-DLL4, a cancer therapeutic with multiple mechanisms of action, demonstrated improved anti-tumor and immune responses in different mouse models of tumors when combined with anti-VEGF and anti-PD1.
The data was presented at this year’s Society for Immunotherapy of Cancer (SITC) Conference in a poster entitled “Co-Targeting of Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF) with Programmed Death 1 (PD1) blockade inhibits tumor growth and facilitates anti-tumor immune responses” by Angie Park, PhD, Director of Immunotherapy and Stem Cell Biology at OncoMed Pharmaceuticals.
DLL4 plays key roles in regulating cancer stem cells, tumor angiogenesis (the ability of a tumor to stimulate new blood vessel formation) and pro-tumor immune responses. In a series of preclinical studies, researchers investigated the impact of anti-tumor immune responses with two different treatments, either anti-DLL4 combined with anti-VEGF, anti-DLL4/VEGF or the triple combination of anti-DLL4/VEGF/PD1 (an immune checkpoint that down regulates the immune system by preventing T cell activation). Triple blockade of DLL4-VEGF-PD1 enabled potent anti-tumor immune responses and lead to a significant reduction in tumor growth, when compared to DLL4/VEGF combination or each component administered alone.
Additionally, the research team observed that adding anti-DLL4/VEGF also led to an improvement in the activity of anti-PD1 alone in mouse models of PD1 responsive and non-responsive tumors.
Austin Gurney, PhD, Senior Vice President of Molecular and Cellular Biology, commented these preclinical results in a press release: “These data highlight the ability of the anti-DLL4/VEGF bispecific to combine with anti-PD1 and to modulate anti-tumor immune responses. In addition to increased anti-tumor efficacy, we note enhanced generation of memory T cell responses and reduced tumor-associated macrophages. These results show that co-targeting of DLL4 and VEGF with PD1 might be an effective and durable anti-cancer therapy in part by promoting anti-tumor immune responses and inhibiting pro-tumor immune responses.”
