Bifunctional Protein-Polymer Bioconjugates for Localized Melanoma Immunotherapy

Project Summary Melanoma is an aggressive form of skin cancer with low survival rates in later stagesparticular once it has metastasized to distant regionsIt is the fifth most commonly diagnosed cancer in the US with an estimatednew cases diagnosed annuallyMelanoma is an ideal candidate for the development of novel immunotherapies that can stimulate the patient s own immune system against the tumor through localized therapy as it is responsive to these types of therapies and accessible for injection directly into the tumorStudies have shown that immune activating cytokines such as interleukinILcan stimulate tumor regression of both the primary injected tumor and distant metastasesHoweverthe range of immune activating cytokines available for clinical use is limitedas the high doses required to induce an antitumor response via systemic delivery can cause severe side effectsEfforts to deliver therapy locally to the tumor are hampered by the rapid diffusion rate of the small cytokinesrequiring frequente gtimes a weekintratumoral injections for effective treatmentTo enable longer acting ILdrug activityValitor has developed a patented platform technology for generating soluble clusters of therapeutic proteins attached to single chain biopolymersIn contrast to other methods of protein polymer conjugatione gPEGylationour method of conjugation generates substantially larger conjugates with enhanced drug potencyConjugate retention within a tumor can be further enhanced by adding copies of a second protein to bind extracellular melanoma specific antigens such as anti melanoma associated chondroitin sulfate proteoglycanMCSPThereforewe anticipate that a bifunctional conjugate made using ILand anti MCSP antibodiesi emvAnti MCSPxILwill be retained within the tumor at leasttimes longer than an unmodified cytokineOur objective during Phase I is to demonstrate proof of concept for our multivalent conjugates to provide a sustained effective intratumoral dose of an immunotherapy with minimal systemic exposure following a single local injectionWe expect this mvAntiMCSPxILtherapy will follow a well defined route to FDA market approval and commercializationwhich we will continue during the next phase of this project Relevance Melanoma is the fifth most common type of cancer in the USand it is a significant public health concern as an estimatednew cases are diagnosed annually and mortality rates increase greatly after metastasisValitor has developed a novel long acting immunotherapy to treat melanoma by enabling a sustained and focused anti tumor immune response following intratumoral injection