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December 01, 2010 (Vol. 30, No. 21)

Delivering Long-Lasting Cancer Vaccines

Immunovaccine Strives to Make Single Doses Last a Decade with Its DepoVax Technology

  • Vaccine Advances

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    Subcutaneos tissue following an injection of DPX-0907 with a significant immune response

    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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