Breast Cancer Vaccines for Primary Prevention Move Toward Clinical Use

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Nora Disis, MD

Combination immune-chemoprophylaxis may significantly improve the protective efficacy of vaccines designed to prevent breast cancer in high-risk populations and postmenopausal women.

—Nora Disis, MD, and colleagues

The first candidate vaccine to prevent recurrence of breast cancer entered clinical trials about 8 years ago, and since then, the idea of a vaccine for secondary prevention has gained traction; more such vaccines are now in development. But this fall, it was vaccines for primary prevention that had the spotlight.

In a study featured at the 12th Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research, held recently in National Harbor, Maryland, investigators tested a triple-antigen vaccine combined with bexarotene (Targretin) in a murine model. The treatment prevented mammary tumor development in 90% of the mice, many of which had preinvasive lesions, reported Nora Disis, MD, who leads the University of Washington’s Tumor Vaccine Group where the vaccine was developed. The researchers are now ready to file their investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA).

Also recently, the Cleveland Clinic announced that it had created a company to move ahead with clinical testing of a preventive vaccine that targets a single protein, alpha-lactalbumin. Vincent Tuohy, PhD, an immunologist at the Clinic’s Lerner Institute and Chief Scientific Officer of the new company, said that his group was preparing for a preliminary IND meeting with the FDA in early 2014.

The two recent developments underline how far cancer vaccines have come in just the past few years. The first treatment vaccine, sipuleucel-T (Provenge) for prostate cancer, won FDA approval 2 years ago. One breast cancer vaccine for secondary prevention, NeuVax, is now in a phase III trial and another, called AE37, is in phase II. Both target peptides of HER2/neu.

Triple-Antigen Approach

The two new primary prevention candidates take different approaches.

At the University of Washington, Dr. Disis’s group had already developed vaccines based on three antigens separately—HER2/neu, insulin-like growth factor binding protein-2 (IGFBP-2), and insulin-like growth factor receptor-1 (IGF1R). They found that each could partially inhibit tumor development in mice, but the three antigens combined in one vaccine were significantly more effective, blocking development of palpable lesions in 65% of mice.

The researchers then tried pairing the triple-antigen vaccine with two therapeutic agents that had been shown to prevent tumor development in mice, lapatinib (Tykerb) and bexarotene. Adding lapatinib proved no more effective than vaccination alone, but in the mice given bexarotene plus the vaccine, 90% had no pathologic evidence of carcinomas at 1 year.

The mice used in the studies were older and many had preinvasive lesions, like the women who might someday be candidates for a preventive vaccine, Dr. Disis said. In the triple-antigen study, published in Cancer Prevention Research in October,1 she and her colleagues concluded that “combination immune-chemoprophylaxis may significantly improve the protective efficacy of vaccines designed to prevent breast cancer in high-risk populations and postmenopausal women.”

The phase I trial of the triple-antigen vaccine—named WokVac in honor of a patient advocacy group called Wings of Karen that raised money to cover its manufacturing costs—could begin by March or April, Dr. Disis said in an interview. Because one of the antigens, IGF1R, has not yet been tried in humans, the vaccine will be tested first in women who already have invasive breast cancer; the phase I trial will determine the safety of that vaccine component, as well as the optimal dose for all three.

Once past phase I, trials will enroll women with abnormal lesions, such as ductal carcinoma in situ, and women at high risk, such as those with BRCA mutations, to test its efficacy in preventing invasive disease.

This group has also been working on a prophylactic vaccine targeted at cancer stem cells, called StemVac. They expect to submit the IND in January or February and to begin trials later in the year, Dr. Disis said.

Targeting Alpha-Lactalbumin

The Cleveland Clinic’s prevention vaccine made news this fall, when Cleveland Clinic Innovations announced that a spin-off company, Shield Biotech, would take the vaccine to trials. Popular media like The Huffington Post and MORE magazine ran articles, raising awareness of cancer prevention vaccines in general and bringing numerous inquiries and pledges of support.

“There’s an eagerness in the patient community,” Dr. Tuohy said. Two Cleveland auto repair companies organized a nationwide effort of 68 auto repair shops in over 23 states that donated 10% of their brake sales during October to the vaccine project.

This vaccine’s target antigen, alpha-lactalbumin, is overexpressed in many breast cancers, but particularly in triple-negative tumors. It is a breast-specific protein normally expressed only in late pregnancy and during lactation. In a 2010 Nature Medicine article,2 Dr. Tuohy and colleagues reported they had vaccinated young mice at high risk for mammary tumors and found, after 8 months, that none had developed tumors. In contrast, all of the control vaccinated mice developed tumors.

Currently, Shield Biotech is working on FDA-required protocols for preparation and manufacture of the vaccine and toxicology studies. The major safety concern with this and other vaccine strategies that use the immune system to target self-proteins is the risk of a systemic, inflammatory autoimmune response.

The researchers are proposing two trials: A phase Ia trial, primarily to determine dosage, frequency, and safety, would enroll women with triple-negative breast cancer who have been treated with standard therapy and are in remission. The phase Ib trial would enroll women at very high risk of breast cancer who have elected to undergo a bilateral prophylactic mastectomy and who receive the vaccine several months before surgery. The removed tissue would be examined for any potential safety issues.

As with the University of Washington vaccine, the ultimate goal is to vaccinate healthy women who are at high risk for breast cancer.

Artemis Project

While many researchers see self-proteins as the key to a prophylactic breast cancer vaccine, some are focusing on infectious agents. The National Breast Cancer Coalition’s (NBCC’s) Artemis Project for a breast cancer prevention vaccine has awarded seed grants to several researchers to search through breast cancer genomes for evidence of infectious agents not found in normal breast tissue.

Half of the funding for the grants comes from the National Philanthropic Trust, but like the Cleveland Clinic and University of Washington projects, the NBCC welcomes donations. A recent YouTube video urges viewers to contribute through RocketHub, the crowdfunding website. “Advocates and scientists are working side by side,” the text of the video reads. “Support NBCC’s Artemis Project... Be a part of history!” ■

Disclosure: Dr. Tuohy is Chief Science Officer of Shield Biotech, Inc, and as such may have a financial interest in this company that has several patent applications related to the vaccine technology he invented. Dr. Disis reported no potential conflicts of interest.


1. Disis ML, Gad E, Herendeen DR, et al: A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res. November 19, 2013 (early release online).

2. Jaini R, Kesaraju P, Johnson JM, et al: An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nat Med 16:799-803, 2010.