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Columns : Dec 1, 2010 ( )
Delivering Long-Lasting Cancer Vaccines
Immunovaccine Strives to Make Single Doses Last a Decade with Its DepoVax Technology!--h2>
Researchers at Dalhousie University in Halifax, Nova Scotia, founded Immunovaccine about 10 years ago. The Canadian government asked them to create a contraceptive vaccine to humanely control seal populations. The resulting vaccine technology was successful not only in seals but also worked on other wild animals including monkeys in Hong Kong.
The scientific challenge for inoculating wild animals was to design a vaccine that needs only a single injection and lasts a decade. "The delivery system was the secret," says Immunovaccine’s president and CEO, Randal Chase, Ph.D.
Now researchers at Immunovaccine in Halifax are applying the same delivery system to human vaccines aimed at cancer and infectious diseases. "There are no human vaccines where a single injection lasts 10 years," notes Dr. Chase.
The company’s DepoVax™ platform consists of vaccine antigens and adjuvants wrapped in liposomes within an oil depot. Liposomes allow more antigen and adjuvant to be injected compared to oil alone, and they hold the antigen and adjuvant together, resulting in a powerful and long-lasting immune response.
When injected, the combination forms a "depot vaccine" that remains active for weeks to months. A single dose generates strong cellular and humoral immune responses. "The delivery system is basically the same for therapeutic and preventive vaccines," Dr. Chase says.
The DepoVax platform reduces the standard two to three injections of a vaccine needed for optimal immunity to just one, and it gives an earlier onset of protection, according to Immunovaccine. The firm says that in preclinical models, a single dose prevented the growth of tumors and up to 100% of cancer cells were destroyed. DepoVax works with a variety of antigens including peptides, proteins, nucleic acids, and synthetic antigens. The dry formulation can be stored and reconstituted for clinical use.
Immunovaccine says its patent protection is broad and covers combinations of any antigen, any adjuvant, and any liposome mixed with any oil. "We have a rocket booster system that enhances the immune response," says Dr. Chase, and "we can boost the immune response of any vaccine."
To prove the advantages of their platform, researchers at Immunovaccine invite other vaccine companies to take the "DepoVax challenge". Companies send their vaccines to Immunovaccine, where they are reformulated free of charge with the liposome/oil delivery system and then returned to undergo head-to-head testing.
"We believe that we can deliver other people’s products better than they can," Dr. Chase says. He notes that for many vaccines, fewer doses are required, because the DepoVax system induces a much stronger immune response. He also adds that the DepoVax challenge has led to licensing agreements on a broad range of applications.
In addition to helping collaborators, Immunovaccine is building an internal pipeline. The company’s lead candidate, DPX-0907, targets breast, ovarian, and prostate cancer. The vaccine contains seven specific peptides found on the surface of ovarian, breast, and prostate tumor cells that are recognized by the immune system and generate key cellular responses. The seven cancer antigens represent six major cancer pathways.
"We’re coming at cancer cells from seven different directions, so they cannot easily downregulate a single protein and escape," Dr. Chase says. Oncologist Michael Morse, M.D., at Duke University School of Medicine, is coordinating Phase I trials of DPX-0907 at sites in the U.S., and safety results are expected by the end of 2010.
A recent preclinical study found that DPX-0907 does not induce undesirable immune responses that favor tumor growth, a problem for most therapeutic cancer vaccines. The immune system plays two contradictory roles in cancer. First, an adaptive immune response, such as by Type-1 CD8+ T-cells, attacks tumor cells. However, a secondary response, such as by regulatory T cells, accumulates at tumor sites and suppresses Type-1 CD8+ T-cell responses.
A major challenge of cancer vaccine design is to enhance the immunogenicity of chosen peptides while overcoming tumor-induced suppressive immune responses. DPX-0907 achieved this goal in a mouse model, as reported in the April issue of the Journal of Immunotherapy.
Other vaccines for Pseudomonas aeruginosa, pandemic flu, and hepatitis B are in early-stage development at Immunovaccine. The vaccine against P. aeruginosa contains a mutated flagellin antigen with potential to protect against several strains of the bacterium.
Tests show that a single dose of the DepoVax pandemic flu vaccine raises a stronger immune response than two doses of the conventional formulation, Immunovaccine claims. Also, the lyophilized product can be stored long term and reconstituted should a flu pandemic hit. The company also notes that a single dose of the hepatitis B vaccine elicits faster, stronger, and longer-lasting humoral responses than conventional vaccines.
Immunovaccine is collaborating with Defense Research and Development Canada to improve a vaccine for anthrax. In animal models, a single dose of anthrax antigen formulated in DepoVax raises antibody levels 10 times higher on average than a comparable alum-adjuvant anthrax vaccine, the firm claims. It says that a single dose induces persistent antibody levels within a month, and the results indicate that DepoVax can reduce the number of doses of anthrax vaccine needed to immunize people from six to one or two.
Vaxil BioTherapeutics in Israel is one of the newest collaborators. Vaxil is developing T-cell synthetic vaccines for therapeutic and prophylactic use. The company’s VaxHit™ technology identifies vaccine candidates for cancer and infectious diseases, and its ImMucin™ vaccine for multiple myeloma is in Phase I/II clinical trials. The combination of the VaxHit and DepoVax technology will advance vaccine development, the companies predict.
On April 29, 2010, the U.S. Food and Drug Administration approved Dendreon’s Provenge, the first immunotherapy for prostate cancer. "This approval confirms that there is a place for immune therapy in the treatment of cancer," says Dr. Chase. "We are building on that by developing cancer vaccines that will play a key role in the treatment of cancer."
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