Newer Vaccine may prevent Triple Negative Breast Cancer for the first time

The Cleveland Clinic has begun clinical testing of a novel vaccine designed ultimately to prevent triple-negative breast cancer (TNBC) by priming high-risk women to mount an immune response against a "retired" lactation protein expressed only in cancer cells reports their official site. The U.S. Food and Drug Administration recently approved an investigational new drug application for the vaccine, allowing the clinical trial to move forward. 

What's Triple negative breast cancer?

TNBC is so-named because patients' cancer cells test negative for estrogen and progesterone receptors and the human epidermal growth factor receptor 2 (HER2) protein, making hormone therapy and HER2-targeted drugs ineffective. It accounts for 12-15% of all breast cancers and is the most aggressive and lethal subtype. Nearly one-quarter of all TNBC patients die within five years of diagnosis; five-year survival in patients with distant metastases is only 12%. TNBC disproportionately affects Black women and women with germline BRCA1 gene mutations. The only effective prophylaxis currently available to women at high risk for TNBC is bilateral mastectomy.

Vaccines for breast cancer

Most breast cancer vaccines presently in development are meant to treat patients with existing tumors or to prevent recurrence in cancer survivors.

Current data indicate that therapeutic vaccines have limited efficacy, at least in part because they employ target antigens that fail to induce a clinically relevant immune response and adjuvants that don't adequately enhance the response. Only one breast cancer vaccine has progressed to phase III trials, and that randomized trial was terminated for futility when interim analysis showed no difference in disease-free survival between the vaccine and placebo.

How this new vaccine is different from the rest?

The prototype Cleveland Clinic vaccine represents a potential new way to combat breast cancer. It is the result of nearly two decades of research by immunologist Vincent Tuohy, PhD, of the Lerner Research Institute's Department of Inflammation and Immunity. Dr. Tuohy persevered despite others' skepticism about his unusual approach and the difficulty of obtaining funding to support years of basic science work to determine the vaccine's feasibility.

"There was a lot of resistance to these kinds of new ideas," he says. "It took a long time for people to think that this vaccine wasn't just pie in the sky — that it was based on good science and was doable."

Dr. Tuohy and his research team chose the breast-specific lactation protein α-lactalbumin as their target vaccine autoantigen because it is no longer found in detectable amounts in normal, aging breast tissues but is expressed at high levels in more than 70% of TNBCs. They verified its expression in human TNBC tissues using molecular and immuno-histochemical analyses.

Dr. Tuohy's experimental vaccine is aimed at primary prevention – stopping cancer before tumors develop.

"We know from the childhood vaccine program that vaccines are to prevent disease," he says. "You don't wait to get polio or measles and then vaccinate. But the entire field of cancer vaccination was using vaccines to treat. And I thought that wasn't right. As a standalone, therapeutic cancer vaccines have not worked well," primarily because of the tumors' substantial head start in growth, the onset of clinical symptoms, the establishment of tumor defenses against the immune response, and the potential for local and distant metastasis.

Because the new vaccine's safety and clinical benefit have not been established in humans, it would be ethically problematic for its initial prevention trial to involve TNBC-at-risk but otherwise healthy women as recipients.

Details of the trial:

the phase I dose-escalation trial will enroll approximately 24 women who are within three years of TNBC diagnosis and currently have stable disease with high risk of recurrence.

In the current trial, participants will receive up to three vaccinations, each two weeks apart, to determine the optimal immunologic dose and the maximum tolerated dose. The women will be closely monitored for side effects and immune response, the latter assessed by blood tests to detect a pro-inflammatory T cell response consistent with tumor protection. The study is expected to be complete in September 2022.

If the initial trial confirms the vaccine's safety and its ability to produce an effective immune response in post-therapy, disease-free TNBC patients, subsequent trials would similarly test it in women who are at high risk for TNBC but have not yet developed the disease.

Source: my.clevelandclinic.org