PURPOSE: The gastrointestinal carcinoma-associated antigen epithelial cell adhesion molecule (EpCAM) has been a target for passive and active immunotherapy of gastrointestinal carcinoma patients. The antigen is expressed by both tumor and normal tissues. The immunogenicity of EpCAM in colorectal cancer patients has been described previously. The purpose of this study was to evaluate humoral and cellular immune responses of healthy individuals and ulcerative colitis patients to EpCAM and to relate immune responses to colonic tissue expression of EpCAM. METHODS: An inhibition radioimmunoassay was used to detect anti-EpCAM serum antibodies. Anti-EpCAM antibodies of a healthy donor were expressed by phages and sequenced. (3)H-thymidine incorporation assay was used for detection of lymphoproliferative responses to stimulation with EpCAM. EpCAM tissue expression was determined by immunohistochemistry. RESULTS: We detected anti-EpCAM serum antibodies in 4 of 10, and EpCAM-specific lymphoproliferation responses in 1 of 10 healthy volunteers. The majority of anti-EpCAM antibodies derived from a healthy donor were germline-encoded. In contrast, none of the 23 patients with ulcerative colitis showed serum antibodies to EpCAM (P=0.005). Antigen expression was greatly reduced and altered in ulcerative colitis patients, whereas colon from healthy individuals and uninvolved colon of colorectal cancer patients expressed high levels of EpCAM. CONCLUSION: The results of these studies suggest an association between EpCAM antibody production and colonic EpCAM expression in healthy individuals and patients with ulcerative colitis. Decreased and altered colonic EpCAM expression in ulcerative colitis patients may be related to the disease induction, based on the previously demonstrated adhesion function of this molecule. Healthy individuals with anti-EpCAM immune responses and high risk for developing colorectal carcinoma are prime candidates for prophylactic immunization against EpCAM.
PURPOSE: The gastrointestinal carcinoma-associated antigen epithelial cell adhesion molecule (EpCAM) has been a target for passive and active immunotherapy of gastrointestinal carcinomapatients. The antigen is expressed by both tumor and normal tissues. The immunogenicity of EpCAM in colorectal cancerpatients has been described previously. The purpose of this study was to evaluate humoral and cellular immune responses of healthy individuals and ulcerative colitispatients to EpCAM and to relate immune responses to colonic tissue expression of EpCAM. METHODS: An inhibition radioimmunoassay was used to detect anti-EpCAM serum antibodies. Anti-EpCAM antibodies of a healthy donor were expressed by phages and sequenced. (3)H-thymidine incorporation assay was used for detection of lymphoproliferative responses to stimulation with EpCAM. EpCAM tissue expression was determined by immunohistochemistry. RESULTS: We detected anti-EpCAM serum antibodies in 4 of 10, and EpCAM-specific lymphoproliferation responses in 1 of 10 healthy volunteers. The majority of anti-EpCAM antibodies derived from a healthy donor were germline-encoded. In contrast, none of the 23 patients with ulcerative colitis showed serum antibodies to EpCAM (P=0.005). Antigen expression was greatly reduced and altered in ulcerative colitispatients, whereas colon from healthy individuals and uninvolved colon of colorectal cancerpatients expressed high levels of EpCAM. CONCLUSION: The results of these studies suggest an association between EpCAM antibody production and colonicEpCAM expression in healthy individuals and patients with ulcerative colitis. Decreased and altered colonic EpCAM expression in ulcerative colitispatients may be related to the disease induction, based on the previously demonstrated adhesion function of this molecule. Healthy individuals with anti-EpCAM immune responses and high risk for developing colorectal carcinoma are prime candidates for prophylactic immunization against EpCAM.
Authors: Sarah Netzel-Arnett; Marguerite S Buzza; Terez Shea-Donohue; Antoine Désilets; Richard Leduc; Alessio Fasano; Thomas H Bugge; Toni M Antalis Journal: Inflamm Bowel Dis Date: 2011-11-13 Impact factor: 5.325
Authors: Sagar J Pathak; James L Mueller; Kevin Okamoto; Barun Das; Jozef Hertecant; Lynn Greenhalgh; Trevor Cole; Vered Pinsk; Baruch Yerushalmi; Odul E Gurkan; Michael Yourshaw; Erick Hernandez; Sandy Oesterreicher; Sandhia Naik; Ian R Sanderson; Irene Axelsson; Daniel Agardh; C Richard Boland; Martin G Martin; Christopher D Putnam; Mamata Sivagnanam Journal: Hum Mutat Date: 2018-11-29 Impact factor: 4.878
Authors: John C Castle; Martin Loewer; Sebastian Boegel; Jos de Graaf; Christian Bender; Arbel D Tadmor; Valesca Boisguerin; Thomas Bukur; Patrick Sorn; Claudia Paret; Mustafa Diken; Sebastian Kreiter; Özlem Türeci; Ugur Sahin Journal: BMC Genomics Date: 2014-03-13 Impact factor: 3.969