Characterization of colon cancer–associated antigens that would be key therapeutic targets in the prevention of disease relapse or progression

Autor: Mary L. Disis, Doreen Higgins, Samuel H. Whiting, Elizabeth K. Broussard, Meredith Slota, Grace Gyurkey, Lauren Rastetter, Rachel Kim, Andrew L. Coveler, Ekram Gad, Jennifer Childs
Rok vydání: 2012
Předmět:
Zdroj: Journal of Clinical Oncology. 30:594-594
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2012.30.4_suppl.594
Popis: 594 Background: Colon cancer (CRC) is an immunogenic tumor and adaptive immunity may play a role in inhibiting disease relapse. A vaccine to boost cellular immunity in CRC patients could prevent disease recurrence, but there have been few defined immunogenic proteins identified as vaccine candidates. TVG has shown that overexpressed tumor associated proteins, abundant in the cancer state but expressed at basal levels in normal cells, can be immunogenic. We hypothesized that ideal candidate antigens would be ones already validated as prognostic markers in multivariate analysis. Methods: From a directed literature review we selected antigens based on (1) incidence of expression, (2) independent predictor of poor prognosis or early disease recurrence, and (3) known biologic function in CRC pathogenesis. We identified peptides that were predicted to be high affinity binders across multiple HLA DR alleles. We evaluated immunogenicity of peptides with IFN-g ELISPOT assays in CRC and control patients. We then evaluated the efficacy of vaccination in reducing tumors in the AOM mouse model. We evaluated immunogenicity of peptides with IFN-g ELISPOT assays using vaccinated mice splenocytes. We quantified antigen protein expression in AOM tumors. Results: The eight proteins are: CDC25B, COX-2, EBAG9, EGFR, Fascin-1, IGF-1R, PRL-3 and VCP. For all candidate antigens there was a greater IFN-g response in CRC patients than in controls. Four antigens (COX-2 p Conclusions: We conclude that: 1. biologically relevant CRC associated proteins can be identified that are associated with prognosis, 2. epitopes predicted to bind multiple DR alleles, derived from candidate antigens, elicit T cell responses greater in CRC patients than in normal controls, 3. vaccination with peptides derived from four antigens resulted in a statistically significant reduction in the development of colon tumors in a mouse model, and 4. these antigens may represent novel immunologic targets for CRC.
Databáze: OpenAIRE
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