Bench-to-bedside challenges in developing immune protection against breast cancer

FROM BENCH TO BEDSIDE

How then do we determine whether alpha-lactalbumin vaccination prevents the development of TNBC in otherwise healthy cancer-free women, and whether it prevents recurrence of TNBC in women already diagnosed with TNBC? Our initial approach will involve two phase 1 clinical trials designed to determine the safety of the vaccine as well as the dose and number of vaccinations needed to induce optimum tumor immunity.

The first (phase 1a) trial will involve vaccination of women recently diagnosed with TNBC who have recovered with the current standard of care. These women will be vaccinated in groups receiving various doses of both recombinant human alpha-lactalbumin and an appropriate immune adjuvant that activates the immune system so it responds aggressively to the alpha-lactalbumin and creates the proinflammatory T-cell response needed for effective tumor immunity. This trial will simply provide dosage and safety profiles of the vaccine and will thereby lay the groundwork for subsequent (phase 2 and 3) trials designed to determine whether alpha-lactalbumin vaccination is effective in preventing recurrence of TNBC in women already diagnosed with this disease.

The dosage and number of immunizations shown to provide optimum immunity in the phase 1a trial will be used in a second (phase 1b) trial designed primarily to determine the safety of alpha-lactalbumin vaccination in healthy cancer-free women who have elected to undergo voluntary prophylactic mastectomy to reduce their breast cancer risk. Most of the women who elect to have this surgery have an established family history of breast cancer or a known BRCA1 mutation associated with high breast cancer risk, or both.^11,12 Consenting women will be vaccinated against alpha-lactalbumin several months before their mastectomy, and their surgically removed breast tissues will be examined extensively for signs of vaccine-induced autoimmune damage. Thus, this trial will determine the safety of alpha-lactalbumin vaccination in healthy cancer-free women and will lay the groundwork for subsequent phase 2 and 3 trials designed to determine whether alpha-lactalbumin vaccination is effective in preventing TNBC in women at high risk of developing this form of breast cancer.

We estimate that completing our preclinical studies, obtaining permission from the US Food and Drug Administration to test our investigational new drug, and completing both phase 1 clinical trials will require about 5 years. Thereafter, completion of phase 2 and 3 trials designed to prevent both recurrence of TNBC in women already diagnosed with this disease and occurrence of TNBC in otherwise healthy, cancer-free women will likely take at least another 5 years, so that this vaccine will likely not be available to the general public before 2024.

TO SUM UP

Although our immune system is potentially capable of protecting us from some cancers, we currently have no immune protection against cancers we commonly confront as we age. We propose that tissue-specific self proteins that are retired from expression with age in normal tissues but are expressed at immunogenic levels in emerging tumors may substitute for unavailable pathogens as targets for immunoprevention of adult-onset cancers that commonly occur with age. We know that the retired breast-specific protein, alpha-lactalbumin, is overexpressed in TNBC and that vaccination with alpha-lactalbumin provides safe and effective protection from breast cancer in preclinical mouse studies. Clinical trials are planned to ultimately determine whether alpha-lactalbumin vaccination can prevent recurrence of TNBC in women already diagnosed with this disease and prevent the initiation of TNBC in women at high risk of developing this most aggressive and lethal form of breast cancer.
 

Acknowledgment: This work was supported by a grant from Shield Biotech, Inc., Cleveland, OH. In addition, the author wishes to recognize and express his sincere gratitude for the support and encouragement received from numerous organizations that have been instrumental in making this work possible, including November Philanthropy, Brakes for Breasts, the Breast Health and Healing Foundation, the Toni Turchi Foundation, the Coalition of Women Who Care About Breast Cancer, the Sisters for Prevention, the Previvors and Survivors, the Champions of the Pink Vaccine, the Race at Legacy Village, the National Greek Orthodox Ladies Philopto-chos Society, the Daughters of Penelope Icarus Chapter 321, Can’t Stop Won’t Stop, the Babylon Breast Cancer Coalition, and Walk With A Doc.