Mucin-1 (MUC1) is a tumor-associated antigen expressed in many human adenocarcinomas including breast cancer, ovarian cancer and hematological malignancy. Novel approaches based on exploiting the power of dendritic cells to program the immune system are an important approach to making such cancers treatable. Considerable emphasis has been placed on defining tumor-specific antigens and delivering them to dendritic cells to establish a clinically efficacious response. The system we have developed has the potential to deliver antigens directly to dendritic cells in vivo without the need for ex vivo procedures. Using this novel system, we are developing a novel tumor immunotherapy based on the recombinant particulate antigen delivery system designated the Advanced Antigen Presentation Platform (AAPP), and a peptide from the adenocarcinoma cancer associated protein, MUC1. AAPP has been engineered to deliver disease-specific antigens to prime the cellular and humoral immune system to recognize and neutralize the disease associated with the delivered antigen. In the case of MUC1, a region known as the variable number of tandem repeats (VNTR) encodes a 20 amino acid repeating segment that has been shown to contain peptides with affinity for MHC class I receptors. A 40 amino acid peptide representing VNTR has been cloned into AAPP for delivery and designated AAPP-MUC1. Our specific goals are: 1) analyze the humoral and cellular immune response of AAPP-MUC1 in control as well as transgenic mice expressing human MUC1; and, 2) evaluate the prophylactic and therapeutic effect of AAPP-MUC1 on MUC1 expressing tumors in control as well as transgenic MUC1-mice. Development of immunotherapies utilizing a combination of model systems, as proposed in this phase I proposal, is crucial to finding effective treatments for adenocarcinoma.
| Gathuru, John K; Koide, Fusataka; Ragupathi, Govind et al. (2005) Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity. Vaccine 23:4727-33 |
