A spinoff business launched by a University of Wisconsin-Madison cancer researcher is attempting to harness the human immune system to fight prostate cancer.
Prostate cancer kills almost 30,000 American men each year, making it the second-biggest cancer killer of men. If the cancer is not fully eradicated by radiation or surgery, it may resume its slow growth for several years. During this period, treatment is usually suspended until the PSA (prostate specific antigen, a blood marker for the cancer) resumes its rise, and imaging detects new tumors.
Douglas McNeel, a professor of hematology and oncology at UW-Madison, observes that the suspension of treatment provides a window to test a treatment designed to trigger an immune response to PAP (prostatic acid phosphatase), a molecule found only on prostate cells.
McNeel notes that the Food and Drug Administration has already approved another prostate cancer vaccine that also targets PAP, but that vaccine uses a “cumbersome means of delivery” and is approved for patients with more advanced disease.
In an ongoing phase II trial of the PAP vaccine that McNeel initiated, vaccine treatments begin after the initial surgery and/or radiation is completed and patients show rising PSA. Ideally, the vaccine will delay the recurrence of metastatic cancer, perhaps so long that the man will die of another cause.
But federal funding is tight, and, McNeel says, “No matter what we see, the 56-patient study is too small to be convincing.” In 2012 McNeel and Richard Lesniewski started Madison Vaccines Inc. to seek financing to expand that trial.
On Monday, Jan. 13, the company announced that it had raised $8 million from Wisconsin Alumni Research Foundation, the State of Wisconsin Investment Board, Venture Investors, LLC and Venture Management, LLC, and other sources.
Much as the annual flu vaccine “presents” flu proteins to the immune system that identifies them as enemies, cancer immunotherapy presents to immune cells a target that occurs mainly or solely on cancer cells.
Immune therapy for cancer is progressing quickly, with new agents approved and many trials already started against advanced melanoma, kidney cancer and non-small-cell lung cancer. “Immunotherapy is showing a benefit in multiple diseases because it does not target particular cancer types; instead it ‘trains’ the immune system,” McNeel says.
This December, Science magazine named cancer immunotherapy the number one scientific breakthrough of the year.
McNeel is also investigating a vaccine that trains the immune system to recognize the androgen receptor, the key protein that binds male hormones like testosterone — as a second vaccine target. Eventually, he’d like a vaccine that sparks attacks on multiple targets. “If we target one protein, the tumor is likely to respond by ceasing the production of that protein, but it can’t turn off something that is driving its existence, like the androgen receptor,” McNeel says.
For similar reasons, multiple agents are already used for treating cancer, AIDS and tuberculosis.
While many vaccines contain inactivated pathogens (flu vaccine, for example, uses parts of viruses), McNeel has inserted genes for his targets into a ring, or plasmid, of DNA. “Plasmid DNA is stable and easy to make, and we think it is more beneficial for generating the kind of immune response we want,” McNeel says. “When the plasmid gets inside a professional antigen-presenting cell, it stimulates immune T cells that are responsible for killing tumor cells.”
Waisman Biomanufacturing, located at the Waisman Center on the UW-Madison campus, played a key role in vaccine development by enabling efficient production, and is working to manufacture the androgen receptor vaccine, says director Derek Hei. “This is a great example of how we can translate scientific discoveries for early stage clinical trials by developing manufacturing and quality control processes in conjunction with product development and regulatory support.”
McNeel is not looking for a home run just yet in the battle against prostate cancer, but rather a solid base hit. “In rodents, with the vaccine alone, you rarely see a tumor shrink, but you do see them grow more slowly, and that is what we believe we have seen in the first human trials.”
Prostate cancer is both a target of opportunity — that slow growth makes it ideal for testing therapies like vaccines that might take time to work — and a passion for a medical doctor who views its real-world toll first-hand. “I look at it as an opportunity to understand, how do we generate a therapeutic long-term immune response?” McNeel says. “But I treat patients, and the prospect of finding something to delay prostate cancer progression is definitely a motivator.”
And that explains his hopes for Madison Vaccines. “This is a partnership between our academic goal to understand human immunology and how tumor vaccines work, and our practical goal to develop better treatments for patients with prostate cancer.”
McNeel says the ongoing story illustrates the strong partnerships that are fostered and built in Wisconsin, “bringing together a UW-Madison investigator, Wisconsin-based ventures to create a UW-spinoff, with product produced by Waisman Biomanufacturing, a UW-Madison resource. This is another example of Wisconsin’s increasingly robust support for innovation in therapeutics development.”