title: Combined staining of TAG-72, MUC1, and CA125 improves labeling sensitivity in ovarian cancer: antigens for multi-targeted antibody-guided therapy.
abstract: Single antigen-targeted intraperitoneal radioimmunotherapy for ovarian cancer has shown limited success. Due to the heterogeneous expression of tumor antigens on cancer cells, a multi-antigen targeting approach appears logical to augment the therapeutic efficacy of antibody-guided therapy. In the interest of developing this novel approach, ovarian cancer tissue microarray slides containing cancer and benign/non-neoplastic tissue samples (n=92) were processed for single-, double-, and triple-antigen labeling using antibodies for the tumor-associated antigens TAG-72, MUC1, and CA125. Among all ovarian cancer types, 72%, 61%, and 50% of the samples showed immunolabeling for TAG-72, MUC1, and CA125, respectively. Expression level of these antigens was significantly (p<0.005) higher in advanced stage carcinomas compared with early stage. Of the 48 epithelial ovarian cancer samples, individual anti-TAG-72, MUC1, and CA125 antibody probing showed labeling in 89.5%, 87.5%, and 73.0% of the cases, respectively. In the majority of the cancer samples (>70%), a heterogeneous labeling pattern was observed (only 30-40% of the cancer cells within the sample were labeled). However, upon combining the three antigens (triple-antigen labeling), 98% of the epithelial ovarian cancer samples were labeled and >95% of the cancer cells within each sample were labeled. Our data indicate that the heterogeneous expression of cancer antigens appears to be a major obstacle in antibody-guided therapy, and this can be overcome by multiple antigen targeting. Therapeutic efficacy of antibody-guided therapy for ovarian cancer treatment will be enhanced by the combined targeting of TAG-72, MUC1, and CA125.
authors.affiliation: Cancer Biology Research Institute, Sanford Research/USD, Department of Obstetrics and Gynecology and Basic Biomedical Science Division, Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD 57105, USA. subhash.chauhan@usd.edu
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: Namita
authors.initials: N
authors.lastname: Vinayek
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maher
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bell
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Dunham
authors.forename: Michael D
authors.initials: MD
authors.lastname: Koch
authors.forename: Yuhlong
authors.initials: Y
authors.lastname: Lio
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
mesh_terms: D000906:Antibodies; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018394:CA-125 Antigen / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D010053:Ovary / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D004337:Drug Carriers; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; C047052:tumor-associated antigen 72