Independent Research Proposal
This proposal contains a synthesis to make a class of anti-cancer compounds for a potential immunotherapy treatment. We propose a new form of antibody drug conjugate that uses polyoxometalates (POMs) as a drug payload to increase the efficacy of oncolytic viruses for cancer treatment. Oxovanadates have a synergistic effect with oncolytic viruses; they increase replication by inhibiting the immune system that would normally target the virus. However, vanadates react with bio metabolites under physiological conditions, limiting its potential use. To achieve maximum effect of the vanadates without side reactions we will use a cluster of vanadate with an antibody transport system that will transport the polyoxometalate to the cancer site before they fall apart. To achieve this, we will combine peptide chemistry techniques and polyoxometalate chemistry to design linkers that can bind to both the antibody and the polyoxometalate, functionalize the POM to be able to bind to linkers, and bind the anionic metal linker complex to the antibody. We are proposing to synthesize an antibody drug conjugate that contains a polyoxometalate, a linker, and a chosen antibody. The drug payload will be the polyoxometalate in the form of decavanadate or another lacunary polyoxometalate, the linker will be a peptide or a polyethylene glycol type linker and the antibody we have chosen is Bevacizumab.