The Vaccine Story

Phase I Trial of an Alpha-Lactalbumin Breast Cancer Vaccine

 

This trial is based on the “Retired Protein Hypothesis,” first advanced by the late Dr. Vincent Tuohy.  Dr. Tuohy proposed that as we age, we stop producing certain proteins that are no longer needed, such as the pigment in our hair, and the lactation protein in this vaccine called alpha-lactalbumin (aLA). This protein is normally only expressed in breast tissue during lactation. It also re-emerges in certain breast tumors, especially triple-negative breast cancer (TNBC), which we know is the most aggressive and lethal form of the disease and is among the most difficult to treat.

 

Laboratory studies with mice showed that vaccination against alpha-lactalbumin could delay the growth of established breast cancers and altogether prevent the production of breast cancers in some mice who had a high risk of developing breast cancer. Studies indicate that about 70% of triple-negative breast cancer (negative for estrogen-receptor, progesterone receptor, and HER2) express alpha-lactalbumin. 

 

The goals of our Phase I clinical trial were to determine:

1.    Whether we could safely deliver the alpha-lactalbumin vaccine to women who had completed treatment for operable triple negative breast cancer or who were at high risk to develop breast cancer due to genetic factors.

2.    Whether vaccination could produce an immune response to alpha-lactalbumin.

 

What We Showed:

We studied 35 women, 26 who had completed standard therapy for high-risk triple-negative breast cancer (TNBC), 4 who carried a BRCA gene putting them at risk for breast cancer and electing to undergo preventive bilateral breast cancer, and 5 women who received pre-operative chemotherapy and pembrolizumab immunotherapy and who continued to receive pembrolizumab post-operatively during the vaccination period. 

 

Adverse events at Dose Level 1 were generally mild and consisted primarily of lumps, itching, tenderness, or redness at the injection sites.  Higher doses produced small ulcers or skin breakdown that appeared at the injection sites.  These lesions healed over time, but we felt that skin breakdown would not be acceptable to healthy patients trying to prevent breast cancer.  Therefore, we concluded that Dose Level 1, which produced an immune response in most patients, would be best. No other adverse events related to the vaccine were observed.

 

Overall, about three-quarters (74%) of patients developed the intended immune response which was determined by the number of T cells reacting specifically to alpha-lactalbumin. The T cell response was measured by the production of the inflammatory markers interferon-gamma (IFNγ) and interleukin-17 (IL-17).

 

Our poster illustrates that we met the major goals for the alpha-lactalbumin vaccine in Phase I by demonstrating that the vaccine was well tolerated, and effective in producing the intended immune response at Dose Level 1.

 

What We Did Not Show:

A Phase I trial such as this is designed only to establish the safety and optimal dose of the drug. Efficacy, or whether or not the vaccine can prevent TNBC or the recurrence of TNBC will be tested in Phase II.

 

The Future:

Future Phase II and Phase III studies are planned to determine if the aLA vaccine actually prevents or delays breast cancer recurrence or development.  We will address further questions such as:

·         Whether booster shots are needed.

·         Whether some people respond better to the vaccine than others.

·         Why, and when, and how this vaccine is best given.