CytImmune Sciences, Inc., United States
pp. 126 - 129
Keywords: tumor microenvironment, TNF, vascular disrupting agent
The treatment of cancer remains an ever-growing problem. Treating solid tumors as a medical disease first, using the natural biology of tumors to reduce or eliminate tumors in situ, offers patients and the entire healthcare community an opportunity to dramatically improve outcomes and bring 21st century medicines to the most patients worldwide. As solid tumors grow, the new blood vessels supporting that growth are leaky, with fenestrations ranging in size from 0.2-1.2 µm. This unique biology provides an ideal opportunity for systemically administered nanoparticle-based medicines (nanomedicines), ranging in size from 10-100 nm, to target tumors by exiting the circulation through these fenestrations, potentially resulting in improved biodistribution, bioavailability, safety and efficacy. However, other similar or smaller-sized blood components also leak into the tumor interstitial space, creating an interstitial pressure gradient in tumors, where the fluid pressure inside the tumor is greater than it is outside the tumor. This high interstitial fluid pressure (IFP) creates a physical barrier, preventing systemic cancer treatments, such as nanomedicines, from reaching their target, the cancer cells. By design, if a nanomedicine is able to destroy tumor blood vessels, then, using the tumor targeting mechanism noted above, treating cancer patients systemically with such a nanomedicine prior to surgery could eliminate the high tumor IFP. And, if this construct is also carrying a chemotherapeutic agent, then the exposed cancer cells might be more effectively killed. CYT-6091 and CYT-21625 are two nanomedicines designed to take advantage of the biology of tumor necrosis factor alpha (TNF) to induce apoptosis of tumor neovasculature endothelial cells, causing vascular disruption in the tumor and reducing IFP. And, for CYT-21625 it is also designed to deliver paclitaxel directly to tumors. This presentation will focus on a formulation development matrix used to streamline the optimization of these final drug products and the analytical tests used to interrogate them and their components.