Production Of Anti-Cervical Carcinoma Antigen (cca) Monoclonal Antibody And The Distribution Of Cca-Positive Cells

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)


Microbiology and Immunology


Six murine monoclonal antibodies were prepared by using the mouse myeloma cell line Sp2/0-Ag.14 with splenocytes from 4 mice immunized with either a homogenate of human cervical neoplasias or a human squamous cell carcinoma grown in an athymic mouse. Each fusion yielded at least one antibody which was detected to react on cervical tumors and not normal tissues.Conditioned media from 218 hybrid colonies were screened by both immunofluorescent and immunoperoxidase staining techniques on touch preparations of both normal and cancerous human cervix. One monoclonal, 14-3, was chosen to be employed in a blind study as the primary antibody in the staining of cervical smears and a variety of paraffin embedded tissues.One hundred twenty cervical smears, previously stained and evaluated by the Papanicolaou staining procedure demonstrated a false negative staining rate of 2.2% and false positive rate of 41.8%. The differentiating cell type metaplasia, accounted for this relatively high percent of positives.The 14-3, anti-cervical carcinoma antigen (CCA) monoclonal antibody, demonstrated a high degree of specificity for abnormal pathologies of the human cervix. One hundred percent (22/22) of specimens tested were positive for both atypical metaplastic, dysplastic, carcinoma in situ, and invasive carcinoma cell types. Normal tissue and morphologically normal tissue adjacent to atypical cell types were found to be non-reactive with the anti-CCA.Additional tissue types displaying either normal, atypical or neoplastic pathologies were also utilized to study the distribution of the CCA. The 14-3 monoclonal antibody reacted with epithelial cell tumors of the breast, colon, bladder, lung, liver, gallbladder, kidney and other gynecological tumors. No reactivity with normal cell types other than metaplasia was noted. The embryonic origin of the tumor was of no consequence. CCA appears to be distinct from the common oncofetal antigens; carcinoembryonic antigen, (beta)-oncofetal antigen and (beta)-fetoprotein.Further studies into the 14-3 monoclonal antibodies applicability as a screening or prescreening immunological marker are necessary. Preliminary studies indicate it may be quite beneficial in the elimination of negative cervical smears allowing cytotechnicians and pathologists more time to focus on the positive specimens. Additionally the biological significance of this "differentiation" antigen may be of greater importance than its' clinical relevance.


Biology, Microbiology

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