Prevention of colitis-associated colon cancer using a vaccine to target abnormal expression of the MUC1 tumor antigen.
Association between chronic inflammation and cancer development is exemplified by inflammatory bowel disease (IBD) where patients with chronic uncontrolled colitis have a significantly increased risk of developing colitis-associated colorectal cancer (CACC). CACC appears to progresses through the inflammation-dysplasia-carcinoma sequence. This highlights the need to identify targets and interventions that reduce inflammation and prevent development of dysplasia in the context of IBD. Using the dextran sulfate sodium (DSS) mouse model of chronic colitis and CACC, we show that an important target of intervention in human disease would be the epithelial cell molecule MUC1 that is aberrantly expressed on inflamed colonocytes and promotes inflammation and progression to CACC. We show that a MUC1 vaccine can ameliorate chronic colitis and prevent development of dysplasia in the colon and thus extend survival in human MUC1 transgenic mice. This study supports the potential of prophylactic vaccines to target antigens that become aberrantly expressed in chronic inflammation (e.g., IBD) and continue to be expressed on the associated cancers (e.g., colon cancer), to prevent and/or treat both diseases.
Department of Immunology; University of Pittsburgh School of Medicine; Pittsburgh, PA USA ; Division of Pediatric Pathology; Children's Hospital of Pittsburgh; Pittsburgh, PA USA.
Pamela
P
Beatty
Sarangarajan
S
Ranganathan
Olivera J
OJ
Finn