Preclinical and Clinical Studies of MUC1 Glycopeptide Vaccine Strategies in Breast Cancer

Investigators: Mayo Clinic Cancer Center - Sandra Gendler, Ph.D.; Svetomir Markovic, M.D., Ph.D.; Pinku Mukherjee, Ph.D.; James Ingle, M.D.; Timothy Hobday, M.D.; and Daniel McCormick, Ph.D.

In Project #3, the researchers are developing a vaccine that attacks tumors which have started or prevents them from starting. Mayo researchers will first attempt to identify the most effective antigen—something that causes the body to produce a type of white blood cell that can kill tumors, called tumor-specific cytotoxic T lymphocytes (CTLs).

In searching for an effective antigen, Mayo researchers are focusing on the role of glycopeptides, short chains of amino acids with sugar molecules attached to them. The glycopeptides are part of MUC1, a protein found at very high levels on most breast tumors. MUC1 is an oncoprotein, a protein that promotes tumor formation. Some glycopeptides have the ability to stimulate the immune system to help attack and get rid of foreign invaders or tumor cells. Mayo researchers are trying to identify which parts of the MUC1 protein have the best antitumor effect and can create a long-term immune memory—so that immunization with this glycopeptide will have tumor-killing or inhibiting abilities.

Mayo researchers will test the effectiveness of this vaccine against breast tumors in mice and translate the most effective immunization strategy into a clinical trial in patients with breast cancer. They will also determine the optimal time following primary cancer therapy for administration of the vaccine.

The development of a MUC1 glycopeptide vaccine has several potential benefits: to control breast cancer, to prolong the time to recurrence, and, ultimately, to serve as a preventive measure in high-risk individuals.

Project 3 involves expansion of collaborations between research conducted in a number of Mayo Clinic Cancer Center laboratories into an effort to generate an even more effective vaccine towards MUC1. Work in Dr. Gendler’s and Dr. Mukherjee’s laboratories has already identified a range of new molecules derived from MUC1 that have different sugars (glycosylation) attached to the protein back-bone which result in more effective anti-tumor immune responses. The investigators are currently testing which of these would be best suited for further clinical testing.

Building on the experience of the above-mentioned clinical trial of peptide based MUC1 vaccines, the follow-up study will use the best sugar-modified (glycosylated) or anchor-modified MUC1 vaccine with the best immune boosting cocktail (adjuvant) identified in the prior clinical study. This project will also attempt to understand the best markers for predicting a good immune response that could be used to optimize the time of vaccine delivery relative to primary therapy (surgery, chemotherapy, radiation therapy) of breast cancer. The researchers anticipate that they will be able to develop the new clinical trial and begin experimental treatment within the next 24 months. If the latter vaccine proves to be more effective in generating immune responses to MUC1, there will be a subsequent large therapeutic clinical trial utilizing the best MUC1 vaccine in a greater number of patients looking to improve survival. The potential benefit of an effective vaccine against breast cancer is particularly hopeful because it would be harnessing the patient’s own immune system.