MUC1 and Cancer Immunotherapy

MUC1 is a glycosylated transmembrane protein. In normal cells, it is expressed in the apical surface of epithelial cells. Cancer cells express up to 100-fold more MUC1 protein than normal cells. In addition, cancer cells usually have abnormal glycosylation of MUC1 protein. MUC1-associated antibody production and cellular immune responses have been shown to exert a positive effect on cancer patient outcomes. Therefore, boosting MUC1-associated immunity through the use of vaccines, MUC1-specific antibodies, or T cell transfers represents an important strategy in the fight against cancer. Over the past three decades, different types of MUC1-based vaccines have been developed, both in preclinical experimentation and clinical trials. These vaccines include peptide/protein vaccines, vaccinia virus vaccine, dendritic cell based vaccine, and DNA vaccine. In the process of attempting to enhance the immune responses to the vaccines, vaccine carriers such as mannan, keyhole limpet hemocyanin, and adjuvants including Bacillus Calmette-Guerin, incomplete Freund's adjuvants, and saponin, were all tried along with the vaccines with varied successes. We reviewed the literature and presented findings from both preclinical studies and clinical trials related to MUC1 immunotherapy. We also discussed strategies to boost the immune responses, which included the pretreatment with low dose cyclophosphamide before vaccine administration as a Treg suppressive strategy. New evidence and hypotheses are emerging on the effectiveness of MUC1 vaccines in treating subsets of cancer patient population. Those include that innate preimmune status of individual patients may predict benefits of MUC1-based immunotherapy and that Tamoxifen, but not aromatase inhibitors, in combination with MUC1 immunotherapy benefits estrogen receptor positive breast cancer patients. Encouraging results from these hypotheses driven clinical studies added a breath of fresh air into the field of MUC1 cancer immunotherapy. Future success of MUC1 immunotherapy may also reside in the combination strategies of its use with chemotherapy, targeted therapy, and hormone therapy.