SynCon® immunotherapies: powerful antigen-specific immune responses

Inovio’s antigen-targeting immunotherapy technology is designed to activate immune responses against specific targeted cancers or infectious diseases. In certain cases, they are specially designed to help break the immune system’s tolerance to cancer or provide universal protection against unmatched, rapidly mutating viruses.

The elegance of Inovio’s SynCon® immunotherapy technology is that we are not creating an immunogen that would then be placed into the body to induce a desired immune response. Instead, we create a fragment of DNA to produce one or more targeted antigens and place that DNA into cells of the body (with the assistance of our proprietary electroporation systems) where it does nothing other than give instructions to the cells to produce the desired antigen. This approach results in the body creating an immunogen capable of inducing strong, multi-faceted immune responses similar to immune responses to actual cancers or pathogens.

Our design process looks like this:

  • Select appropriate antigen targets for a particular disease.
  • Select multiple variants or strains of the targeted cancer or infectious disease and obtain the DNA sequences from their slightly differentiated antigens. This process is depicted in the illustration below.
  • Pick the amino acids, which make up the DNA, that are the most immunologically conserved, dominant or important.
  • Synthetically create a new consensus gene sequence for the antigen based on the different variants or strains. (Because it does not exist in nature, this sequence is patentable.) The DNA sequence cannot replicate and is not able to cause the disease.
  • Insert this DNA sequence into a DNA plasmid. This is our SynCon vaccine or immunotherapy.

Then what?

We inject the immunotherapy into a patient. Once the DNA plasmid gets into cells in the body, the cellular machinery that is normally used to produce useful proteins for the body’s functioning instead produces our targeted antigenic proteins using the genetic blueprint we provided in the DNA plasmid. These antigens are then presented to the immune system, which activates the production of antibodies and/or killer T cells specific to the targeted cancer or infectious disease.

Our approach has many advantages.

    • We can create antigen-targeting immunotherapies against any cancer or infectious disease.
    • Our SynCon® immunotherapies activate – in vivo - strong T-cell responses (both CD4+ and CD8+). These T-cells are vital to fighting cancerous cells and chronic infections.
    • They can be designed in weeks instead of months or years.
    • They are manufactured by a fast and efficient fermentation process.
    • They are stable at room temperature.

What do the results look like?

Inovio’s SynCon® immunotherapies have, in phase I human studies for cervical dysplasia and HIV generated, best-in-class T-cell responses that are targeted, robust in magnitude, persistent, and functional.

In a phase II study, Inovio’s immunotherapy for cervical dysplasia demonstrated for the first time that a DNA-based immunotherapy can activate CD8+ T-cell responses with a killing effect on the targeted cells and potentially reverse disease progression to cervical cancer. We are advancing this program toward a phase III study.

In an ongoing phase I/II head & neck cancer study of our immunotherapy for HPV-associated cancers, we reported interim data showing significant CD8+ T cell responses in 3 of 4 patients. These positive results represent the first study and first report of T cell immune responses generated in cancer patients after treatment with an Inovio DNA immunotherapy.

In infectious diseases, we achieved proof-of-principle in human influenza studies for the concept that our SynCon sequences could provide cross-strain protection against mutated, unmatched strains of a virus.

Importantly, human data to date has shown our approach has a positive safety profile without a single serious adverse event to date.

Inovio SynCon® Vaccines: from Bug to Vaccination

Targeted antigen production (multi-antigen, if desired) in the body, induces preventive antibody and therapeutic T-cell immune responses.