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Australia: Double Play

Immunotherapy delivered with a one-two punch

It has always been a good idea: direct the body’s immune system to destroy cancer in the same way that it already rids the body of foreign invaders. But making it work has always been the challenge.

The emergence of Seattle-based Dendreon’s prostate-cancer vaccine—approved by the US Food and Drug Administration in 2010—elevated interest in cancer immunotherapy, and Australia’s Ascend Biopharmaceuticals is now building on that success with its cancer immunotherapy vehicle. A new collaboration combines Ascend’s targeted delivery technology with a proprietary immune-system boosting compound developed by 3M Drug Delivery Systems in St. Paul, Minnesota. The combination is intended to generate a two-pronged attack on cancer cells. If successful, it would simultaneously generate antibodies against tumor cells and awaken the arm of the immune system that kills foreign cells on contact. The company is hoping that directing the immune system to treat cancer cells more like pathogens will provide a more robust killing response.

Clinical testing on an early version of the vaccine platform conducted by the technique’s inventors at Austin Research (now the Burnet Institute), in Melbourne, piqued the interest of Ascend CEO Clement Leong. “We’ve taken what was a very tantalizing scientific project and really focused on taking that towards a pathway that would produce a product,” says Leong. “We’ve worked on making sure we have a composition that would be acceptable to regulators.”

A recent follow-up to that small double-blind, placebo-controlled immunotherapy trial against stage-two breast cancer showed two of 16 patients receiving the vaccine had a recurrence, versus nine out of 15 patients in the control group.

Now Ascend is poised to initiate clinical trials that hinge on sensitizing antigen-presenting cells to a sugar-containing protein called mucin-1 found in abundance on cancer cells. A similar sugar polymer, mannan, is present on some infectious pathogens, which makes it an attractive target, since antigen-presenting dendritic cells respond to its presence naturally. Working with the immune system’s inherent triggers has allowed Ascend to generate a potent immune response in preclinical experiments.

The research team is betting that toll-like receptors, which recognize substances produced uniquely by pathogens, conjugated to Ascend’s platform will further boost the effectiveness of the vaccine by initiating an immediate innate immune response, followed by a durable antibody response and killer T cell response to keep cancer in check. “It’s a race between your ability to mount an immune response and the cancer’s ability to grow,” says Leong. “Once it outgrows a certain stage, the cancer just shuts down any prospect for mounting a viable immune response.”

The company plans to initiate clinical trials in Australia based on its improved breast cancer vaccine in 2015, according to Leong. In the past decade, he says the infrastructure and drug development capabilities within Australia have progressed to the point where it’s now possible to design and conduct sophisticated trials. “We are coming of age,” he says.

Toll-like receptors (TLRs) plus an antigen combine with a sugar, mannan, to trigger an immune response that could battle cancer.

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