Mice Transgenic for Human Carcinoembryonic Antigen as a Model for Immunotherapy

摘要: Mice transgenic for the human carcinoembryonic antigen (CEA) gene were prepared use as a preclinical model immunotherapy. A 32.6-kb fragment containing complete CEA and flanking sequences was isolated from genomic cosmid clone used to produce C57BL/6 mice. homozygous line established that designated C57BL/6J-TgN(CEAGe)18FJP. Southern blot analysis showed this contained intact copies of clone, with approximately 19 integrated at one chromosomal location. mouse-human chimeric anti-CEA monoclonal antibody examine expression by immunohistochemical staining frozen tissue sections. In cecum colon, 20% luminal epithelial cells had strong cytoplasmic staining, whereas occasional glands intense staining. also expressed in gastric foveolar cells, small intestine villi only few (<1%) positive cells. not found immunohistochemistry other tissues digestive tract, nor it wide range or organs. Concordance results obtained between extracts enzyme immunoassay. The lone exception testis, which Expression observed derived nontransgenic fecal content mice 100-fold less than humans. Circulating detected. CEA-transfected syngeneic murine colon carcinoma cell line, MC-38, stable vitro vivo. molecular size produced MC-38 similar purified tumors. Anti-CEA appeared but bearing transfected These findings demonstrate distribution its properties are tissues. As humans, immune responsiveness CEA, reflected formation, detectable CEA-positive Thus, may serve useful studying efficacy safety various immunotherapy strategies directed tumor self-antigen.