Abstract 5510: Immunogenicity of the MUC1/Poly-ICLC vaccine in individuals with the history of advanced colorectal adenoma

Abstract

Abstract Background: MUC1 is aberrantly expressed in human adenocarcinomas including colon cancer. Aberrant MUC1 is also found on colorectal adenomas where it promotes malignant transformation by interacting with beta-catenin, ras and other signaling pathways. Induction of immunity against MUC1 during premalignancy may prevent adenoma recurrence and/or their progression to colon cancer. Various MUC1 vaccines, peptide and adjuvant-based, dendritic cell-based or as various viral vectors, have been tested previously in small Phase I/II trials in patients with advanced cancer and have shown low immunogenicity and limited efficacy. In the cancer microenvironment, it is difficult to determine if low immunogenicity is due to the vaccine, to self-tolerance, to the immunosuppressive tumor microenvironement, previous treatments, age of the patient or all of the above. We are conducting a trial using MUC1 peptide and Poly-ICLC adjuvant vaccine in individuals who are cancer free but at high risk for developing cancer because of a recent history of advanced colorectal adenoma. Method: Patients with advanced colorectal adenoma which meets at least one of following criteria, 1) ≥ 1cm in maximal diameter, 2) with villous or tubulovillous histology, 3) with high-grade dysplasia, were vaccinated with 100μg of 100aa MUC1 peptide [H2N-(GVTSAPDTRPAPGSTAPPAH)5-CONH2] admixed with 500μg of Poly-ICLC (TLR-3 agonist) as adjuvant on week 0, 2, 10 and one year later. The primary objective is to evaluate the vaccine immunogenicity (anti-MUC1 IgG and T cell responses) and safety. Results: 43/65 patients have been enrolled. Among 31 patients studied to date, 16 developed anti-MUC1 IgG (52% response rate). This frequency of responders and the high levels of IgG (3-30 fold increase) have never been achieved in cancer patients. Antibody titers declined over time but could be boosted to previous or higher levels at 1 year, showing development of long-term memory. Confirmatory T cell assays are in progress. No adverse events above grade 1 have been identified, and no unanticipated adverse events have been observed. Conclusions: MUC1 poly-ICLC vaccine is highly immunogenic in this prophylactic setting without causing any significant adverse events. Recurrence of adenomas will be evaluated at year 3 and correlated with the immune response, however, a larger randomized trial will be needed to properly evaluate the clinical outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2011-5510