Abstract 5380: Prophylactic MUC1/Poly-ICLC vaccine in individuals with the history of advanced colorectal adenoma

Abstract

Abstract Background MUC1 is aberrantly expressed in a hypoglycosylated form with lack of luminal polarity in variety of human adenocarcinomas including colon cancer. Aberrant MUC1 is also highly expressed in colonic adenomas where it may promote malignant transformation by interacting withβ-catenin known to be an important pathway in colon carcinogenesis. We hypothesized that induction of an immune response against aberrant MUC1 in individuals with a recent history of adenoma may prevent adenoma recurrence and/or their progression to colon cancer. We conducted a clinical study using MUC1 peptide and Poly-ICLC adjuvant vaccine to evaluate the safety and immunogenicity in individuals who are cancer free but at high risk for developing colorectal cancer because of a recent history of advanced adenoma. Method Patients with advanced colorectal adenoma which meets at least one of following criteria: 1) ≥ 1cm in maximal diameter, 2) villous or tubulovillous histology, 3) 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. Bloods were collected two weeks after each injection for monitoring of general immunocompetence, development of anti-MUC1 antibody and safety. Results The vaccine was well tolerated without any adverse event grade 2 or higher. Among 36 evaluable patients, anti MUC1 IgG antibody was elicited in 17 patients as measured on week12 (response rate 47.2%). This response rate and the high levels of IgG have never been seen in response to MUC1 vaccines in cancer patients. Antibody titers declined over time but could be boosted to previous or higher levels at 1 year, showing development of immune memory. Vaccine responders were distributed across most HLA-DR and DQ types with similar frequency as in the general population, indicating that the MUC1 peptide could be presented by multiple Class II alleles. Immune competence of colon adenoma patients evaluated by cytokine production of lymphocyte and regulatory T cell frequency was generally equal to healthy individuals, however myeloid derived suppressor cells (MDSCs) were significantly increased in colon adenoma patients. Increase in MDSCs was especially pronounced in non-responders to the vaccine. Conclusion MUC1 poly-ICLC vaccine is highly immunogenic in this prophylactic setting and no significant adverse events have been seen. Vaccine immunogenicity is reduced in individuals with increased numbers of MDSC and this immunosuppressive population might be used as a biomarker to select patients most likely to respond. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5380. doi:1538-7445.AM2012-5380