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Shield Seeks Preventive Breast Cancer Vaccine

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By Jennifer Boggs
Managing Editor

When it comes to breast cancer treatment, there’s no shortage of drugs in development. Cortellis, the database run by BioWorld’s new parent Thomson Reuters, shows more than 3,500 drugs in development in the space.

But vaccines aimed at preventing breast cancer? Those are much rarer. In fact, “there’s exactly one,” said Pat Fortune, senior manager at Cleveland Clinic Innovations, the commercialization arm of the Cleveland Clinic, which recently spun off Shield Biotech to develop technology from the clinic’s Lerner Institute.

Work on the vaccine was conducted by Vincent Tuohy, Cleveland Clinic immunologist and now chief scientific officer at Shield, with buzzed-about preclinical data published in Nature Medicine in 2010 showing that a vaccine could prevent breast tumors from developing in mice.

Tuohy “had an interesting idea,” Fortune explained. “We all understand how vaccinations are needed to avoid diseases in children. Everyone needs to get vaccinated for polio, measles, diphtheria . . . the standard panoply of disorders children can be exposed to.”

Vaccinations have evolved beyond pediatric applications, as well, most recently with the advent of the human papillomavirus vaccine, he added.

In all those indications, the vaccines are intended to provide proteins to help patients’ immune systems recognize and destroy foreign agents it has not yet encountered, thereby protecting them from disease. But there’s another approach: the retired protein hypothesis, the idea that older patients may have proteins that no longer serve a purpose, “to the point that they are retired,” Fortune said. “But maybe they are useful.”

Shield’s vaccine is designed to target proteins that women produce only in two instances: when they are lactating or when they have active neoplasms. “There was a very natural immunology direction,” Fortune told BioWorld Today.

In their work, Tuohy and his team defined the target antigen, defined an adjuvant and conducted “a lot of meticulous experimental work,” including the Nature Medicine mouse studies.

With money from the National Institutes of Health and philanthropic funding – “a lot of car washes,” Fortune noted – researchers were able to carry the work to the point where there was “sufficient demonstration to form a company to take [the vaccine] into the clinic in the foreseeable future,” which he defined as 12 to 18 months.

Shield is being supported by an undisclosed outside investor. The amount of financing to date also has not been disclosed, though Fortune said it was enough to get through Phase Ia and Phase Ib trials.

Conducting a full-scale preventive vaccine trial would be a costly endeavor for a small biotech, so Shield is planning to start with a treatment study. The protein targeted by its vaccine is up-regulated in a high percentage of triple-negative breast cancer – an aggressive form of the disease that typically carries a poor prognosis.

Triple-negative breast cancer has a higher recurrence rate than other forms, is insensitive to currently available adjuvant therapy and is the predominant form of breast cancers occurring in women with the BRCA1 mutations.

The Phase Ia trial is expected to enroll women with triple-negative breast cancer who have recovered from standard of care (chemotherapy, radiation therapy and/or surgery) to determine dose and frequency of vaccination needed to provide an optimum immune response. Since it’s an immunotherapy, gathering safety information also will be paramount.

Assuming all goes well with that study, Shield expects to move into Phase Ib testing, enrolling healthy cancer-free women who are at high risk for developing breast cancer and who have opted to undergo a voluntary bilateral mastectomy to mitigate that risk. That trial will evaluate safety by examining the removed breast tissue for any potential changes.

“If the vaccine works the way we think it works” – for instance, if antibody titers are observed and remain over a period of time – and safety and signals of efficacy are determined, “then could come larger trials in the same patient population,” Fortune said.

The possibilities for the vaccine are numerous – from potential use in patients at high risk for triple-negative tumors to the prevention of recurrence in patients previously treated to the guarding against metastasis – but it’s too early make predictions. “Obviously, we expect interesting activity in triple-negative breast cancer patients,” Fortune added. “But the data are going to guide the actual pathway.

“Our primary focus is to marshall through the clinic,” he added, work that should keep the primarily virtual firm busy.

“Eventually it is going to require a material clinical trial,” at which time Shield “likely” will seek a partnership, though Fortune said it’s too soon to commit to any specific development plan.

If successful, Shield’s vaccine could be the first vaccine for preventing breast cancer, though there are other therapies aimed at preventing disease. Now generic hormonal therapy tamoxifen has been used to reduce the risk of breast cancer in high-risk patients, and another biotech start-up, Cancer Prevention Pharmaceuticals Inc., is working on a drug comprising low-dose difluoromethylornithine and sulindac in development in familial adenomatous polyposis. (See BioWorld Today, Sept. 1, 2011.)