Inovio Pharmaceuticals, Inc. a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases announced the publication of a scientific paper in the journal Human Vaccines detailing potent immune responses in a preclinical study of Inovio's SynCon DNA vaccine for prostate cancer targeting two antigens. While current prostate cancer therapies target single antigens, in this study Inovio tested the hypothesis in mice that a broader collection of antigens, administered with Inovio's electroporation-based delivery technology, would improve the breadth and effectiveness of a prostate cancer immunotherapy.
The development of a new treatment for prostate cancer would be a significant medical advance given that present treatment options (surgery, radiation and hormone deprivation), while somewhat effective, all carry deleterious side effects and often do not confer long-term cure. Across the United States, there were 218,000 new cases of prostate cancer and more than 32,000 deaths in 2010.
This study, conducted by Inovio scientists and their collaborators, is described in the published paper entitled, “Co-delivery of PSA and PSMA DNA vaccines with electroporation induce potent immune responses.” The SynCon DNA vaccine evaluated in this study was generated by the creation of PSA and PSMA synthetic consensus immunogens based on human and macaque sequences, which enabled the amino acid sequences of the antigens to differ slightly from the native protein.
In humans, this difference may aid in the evasion of self-tolerance while still mounting an anti-tumour immune response. Mice received two immunizations of highly optimized DNA vaccine delivered by electroporation. Immunogenicity was evaluated one week after the second vaccination. The resultant data showed the induction of strong PSA and PSMA-specific cellular immune responses and also significant antigen specific seroconversion, illustrating that both humoral and cellular immune responses can be generated by this approach.
Inovio previously collaborated with the UK's University of Southampton and Institute of Cancer Research in a study evaluating a DNA vaccine for prostate cancer delivered using Inovio's electroporation delivery technology. The published data from this phase I/II study of a DNA vaccine encoding for human PSMA generated proof-of-concept levels of both antibody and T-cell immune responses in the 30 patients vaccinated in this study.
These proof-of-concept results have recently been supported by positive immunology data from Inovio's phase I clinical study of its multi-antigen SynCon DNA vaccine against cervical dysplasia (VGX-3100). In this study, all three dose groups experienced significant antigen-specific antibody and T-cell immune responses against multiple antigens. In the third and final dose group, five of six (83%) patients developed the highest level of T-cell responses achieved by any non-replicating vaccine platform in patients to date.
Dr J. Joseph Kim, Inovio's president and CEO, said: “This is an important study in which the first SynCon DNA vaccine against a cancer target was successfully tested. This immunotherapy targeting more than a single antigen as a treatment for prostate cancer generated strong antibody and T-cell immune responses, which are considered vital to addressing prostate cancer. Taken together with the previous preclinical and clinical data, the current published results support the advancement of this product into a phase I clinical study.”
Inovio's electroporation-based DNA vaccine delivery technology, employed in this study, involves the application of controlled, millisecond electrical pulses to create permeability in the cell membrane and enable dramatic uptake of the vaccine, which has been previously injected into local tissue. Inovio's electroporation-based DNA vaccine delivery systems can increase levels of gene expression (i.e. production of the immune-system-stimulating protein the vaccine was coded to produce) and immune responses of “naked” DNA vaccines by 100-fold or more.
Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. These SynCon vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza.