Immunovaccine personalizes cancer immunotherapies
HALIFAX, Nova Scotia—Immunovaccine Inc. announced in July a significant achievement in its personalized cancer medicines program. Immunovaccine scientists have successfully formulated 14 neoepitope cancer peptides into one DepoVax formulation. In preclinical testing, the resulting personalized cancer vaccine demonstrated the ability to generate specific killer T cell responses against cancer peptides. Immunovaccine has filed a patent application for the DepoVax-based rapid formulation process. The supporting data for the patent includes what the company believes to be one of the first documented reports of 14 different neoepitope peptides synthesized into a single formulation.
This breakthrough evolved as part of Immunovacine's DPX-NEO program, which aims to develop patient-specific immunotherapies targeting neoepitopes. The methodology under this patent application can include peptides with a wide range of physical and chemical characteristics, including those that are insoluble. The company believes this novel process combines the ease and speed of manufacturing with other advantages inherent in DepoVax formulations, including long-term formulation stability and the potential to elicit a strong and specific T cell response maintained for a year or more.
“Despite the promise of leveraging neoepitopes to address cancer, significant barriers to entry have hindered wide-scale research and development,” says Frederic Ors, Immunovaccine’s CEO. “Many of those barriers stem from being able to leverage multiple target peptides in one administration, being able to choose a broad range of peptides to create the best chance for anti-cancer immune responses or the potential expense and logistics of scaling up or down the manufacture of these therapies. DepoVax addresses these limitations, making it the ideal enabling agent for those focused on advancing these types of drug candidates.”
“Synthesizing multiple peptides is notoriously complex, and we believe our work on this front is groundbreaking on multiple levels,” Ors notes. “Our formulation technology gives us the opportunity to become the collaborator of choice with the institutions working to identify and administer neoepitope therapies. The underlying technology behind DepoVax formulations has a track record of producing sustained, highly immunogenic responses, and is easy to scale and manufacture.”
Dr. Marianne Stanford, vice president of research at Immunovaccine, tells DDNews, “DepoVax packages its components into a 100-percent pure oil-based solution, which [is then] injected into a patient. Each DepoVax-based vaccine is comprised of one or more immunologic agents, usually an antigen and an adjuvant, encapsulated in nanoscale lipid particles. DepoVax formulations hold these components at the site of injection, forcing cells of the immune system to interact directly with them. This protects the components from degrading and delivers them right to the immune system, resulting in stronger immune responses.”
“Because DepoVax has the capacity to work with almost any type of antigen or adjuvant, we sought to use the DepoVax formulation technology to deliver multiple neoepitope antigens in a single injection. In our preliminary studies, we were able to formulate all of the peptides that we could have easily synthesized at once (i.e., 14 in this case),” Stanford says.
“In the specific study in which we formulated the 14 peptides, we utilized a set of peptides that had been previously identified in animal models in published literature,” Stanford continues. “But in terms of our ongoing DPX-NEO program, our collaborators are particularly important here because we depend on them to choose the neoepitope peptides, and there are many groups working on optimal approaches to identify the best peptides for delivery. We are currently working with UConn Health, and we are in active discussions to expand the program with additional industry partners.”
Neoepitope vaccines have demonstrated significant potential in the realm of personalized medicines. However, the complexity and potential expense of advancing these patient-specific vaccines includes substantial challenges for development and large-scale deployment. Intensive work is required to identify patient-specific peptide epitopes and synthesize them rapidly into a single formulation. When the neoepitope peptides are selected from patients, investigators have not always been able to include many optimal candidates, due to manufacturing limitations of the technology required to synthesize a single formulation. Immunovaccine believes the DepoVax-based formulations demonstrate the ability to address these limitations. This flexibility should enable investigators to optimize the choices of immunogenic targets access a broader range of candidates.
“We believe that the implications of this formulation process can go well beyond the neoepitope space,” notes Stanford. “We see future applications of the DepoVax multiple peptide formulation using a high number of tumor-associated antigens in one immuno-oncology agent, or multiple targets for an infectious disease within one vaccine. We are excited to explore the potential applications of this technology.”
According to Ors, “We can continue transforming the treatment landscape by expanding the range of patients responsive to these therapies – anti-PD-1, IDO-1 agents, etc. We hope this can be achieved by combining with our clinical candidates—DPX-Survivac and DPX-E7, thus far—and with their demonstrated ability to produce anti-cancer T cells and work synergistically with these other immuno-modulating agents. DepoVax technology has consistently demonstrated the ability to produce strong, sustained, relevant T cell responses.”
“The safety profile and sustained immunological activity of DepoVax-based candidates has been demonstrated in both preclinical studies and human clinical trials in multiple cancer and infectious disease indications,” adds Stanford. “Because of this potential, we’ve already formed strong collaborations with some of the industry’s top players, including Merck, Incyte, Dana Farber Cancer Institute and Leidos.”