Selection of monoclonal antibodies detecting serodiagnostic human tumor markers (original) (raw)
Related papers
Use of four monoclonal antibodies to detect tumor markers
Cancer, 1986
A combined panel of monoclonal antibodies to tumor markers was examined in the sera of 454 cancer patients to compare their reactivity. At least one of the four tumor-associated markers (CEA [caranoembryonic antigen], CA 19-9, CA 125, and SLEX [sialylated Lewisx epitope]) was positive with the sera of breast (43%), lung (64%), ovarian (54%), and colorectal (57%) cancer. Each tumor marker's reactivity was distinct in different patients, indicating that different epitopes were being detected. The number of tumor markers that were positive was associated with advancing stages of disease. In advanced stages with distant metastasis, 13% of the patients reacted with all four markers, whereas none of the early-stage patients did. In 14 cases of disease progression, the tumor markers increased with no instance of decrease. Among ten patients with regression, seven showed a decrease in tumor markers and three showed an increase. The authors conclude that the use of four tumor-associated markers expands the number of patients with a positive marker, thereby permitting the monitoring of some patients. Among 60 normals, one showed a weak reactivity with CEA and one with CA 125. Eventually, with more markers, it should be possible to monitor all patients.
Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies
Proceedings of the National Academy of Sciences, 1979
Fusion of P3 X 63 Ag8 mouse myeloma cells with splenocytes obtained from mice immunized with cells derived from human colorectal carcinomas resulted in the production of antibody-secreting hybridomas. Two hybridomas (1083-17 and 1116-56) and their clones secreted antibodies binding specifically to human colorectal carcinoma cells either grown in culture or obtained from patients, but did not bind to normal colonic mucosa or other normal and malignant human cells. The binding specificity was consistent in three assays: radioimmunoassay, mixed hemadsorption, and immunofluorescence. Adsorption of these antibodies to colorectal carcinoma cell lines totally eliminated their specific binding.
Monoclonal antibodies in the management of carcinoma patients
Medical oncology and tumor pharmacotherapy, 1991
The use of monoclonal antibodies (MAbs) in the clinical management of carcinoma patients is reported in the present review. Among the various MAbs generated, MAb B72.3 (LTIB, National Cancer Institute, U.S.A.) has been extensively used in clinical trials either for antigen identification (TAG-72) in sera, or for tumor localization in carcinoma patients. Serum assay results, in colorectal cancer patients, showed the usefulness of the MAb B72.3 in monitoring the clinical course of the malignant disease. Its specific tumor localization (70% of the biopsy specimens) and the immunoscintigraphy studies, after in vivo administration, have also been discussed. The positive results obtained, markedly contributed in the development of a new intraoperative methodology termed "radioimmunoguided surgery".
Journal of Immunological Methods, 1984
A monoclonal antibody defining the Lewis a blood group determinant was used to immobilize antigen in sera of pa'tients with adenocarcinoma of the gastrointestinal tract, and a second radiolabeled antibody, which defines a gastrointestinal cancer-associated antigen (GICA), was used to detect the immobilized antigen. With this approach, elevated antigen levels were found in 34 of 49 (69%) of sera from patients with advanced colorectal carcinoma as compared with 9 of 292 (3%) of sera from patients with non-malignant gastrointestinal diseases and of healthy donors. For early primary colorectal carcinoma, the combination of anti-Lewis and anti-GICA monoclonal antibodies was more sensitive in detecting GICA than using anti-GICA antibody alone. Double determinant radioimmunoassay revealed the glycolipid determinant lacto-N-fucopentaose (LNF) III circulating in colorectal carcinoma patients' sera. 53% of patients older than 65 years had elevated levels of the LNF III determinant compared to none of age-matched, apparently healthy donors or patients with benign gastrointestinal tract lesions, and 18% of patients with inflammatory gastrointestinal tract diseases. In younger patients, the differences were less marked. Our results suggest the potential usefulness of Lewis and LNF III determinants as markers for the detection of gastrointestinal tract malignancies.
Tumor-associated antigens recognized by human monoclonal antibodies
Annals of Surgical Oncology, 1994
Background: Nonhuman monoclonal antibodies (MoAbs) of desired specificities have been studied in cancer treatment and tumor targeting with minimal success. Attempts of using humanized chimeric antibodies have not improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immunization protocols to the nodal lymphocytes of cancer patients. Three human MoAbs thus generated were found to be strongly reactive with various human malignancies. The antigens recognized by the three antibodies were selected for immunochemical and biochemical characterizations.
International Journal of Cancer, 1989
A series of 14 monoclonal anti-carcinoembryonic antigen (CEA, M, la0,OOO) antibodies (MAbs) that show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues were used to construct a serological map of the CEA molecule. The MAbs were generated using extracts of colon carcinomas as immunogen and are thus given a COL designation. None of the 14 COL-MAbs tested were reactive with purified non-specific cross-reacting antigen (NCA, M, 55,000) from normal lung, although some showed reactivity to human granulocytes. All the COL-MAbs tested were reactive with normal fecal antigen-2 (NFA-2, M, 170,000); however, many of the COL-MAbs demonstrated a higher affinity constant to CEA than to NFA-2. Crosscompetition radioimmunoassays classified the I 4 COL-MAbs into 5 groups. The chemical nature of the COL-binding domains was tested using chemically or enzymatically treated C E A all reacted with periodate-treated CEA and deglycosylated CEA, indicating that the COL-reactive epitopes appear to be of a proteinaceous nature. Heat treatment, reduction, alkylation, pepsin digestion or pronase treatment of CEA, however, gave differential results with respect to COL binding. Antibody titration experiments were carried out to define differential reactivities to colorectal carcinoma versus NCA-containing granulocyte extracts; these results were compared with results obtained using several anti-CEA MAbs that have been used in clinical trials. Granulocyte binding and biochemical studies showed that the COL MAbs may distinguish as many as 7 to 10 CEA epitopes.
Journal of Immunological Methods, 1983
To demonstrate antigens in cultured human tumor cells recognized by antibodies in human sera, extracts of cultured malignant melanoma cells were separated by SDS-PAGE, and electrophoretically transferred to nitrocellulose paper (NCP). The resulting electroblots were incubated with human serum, and bound immunoglobulin (Ig) was visualized with rabbit antibodies specific for human IgG, IgA or IgM, followed by peroxidase-conjugated goat anti-rabbit IgG. Antigen-antibody reactions in the nitrocellulose paper were also detected using 1251-labeled anti-rabbit IgG. As little as 125 pg of bound antibody per band were detectable. The numbers of proteins recognized by antibodies in human sera depended both on the quantity of protein transferred and the concentration of Ig applied to the NCP. Whole serum could not be used at dilutions _~ 1 : 20 without an unacceptable increase in background staining. Binding of Ig to tumor cell proteins transferred to NCP depended on interactions with the Fab', not the Fc region of the Ig molecule. To determine the efficiency of transfer as a function of both time and molecular weight, tumor cell proteins were intrinsically labeled with 75Se-labeled methionine and transferred for up to 4 h after fractionation in gels containing acrylamide concentrations of 5%, 7.5%, 10% or 12%. Proteins < 150 kDa were transferred with particularly high efficiency in _> 2 h. Different antigens were recognized by the IgA, the IgG and the IgM molecules from the same sera. The methods outlined herein are proving to be useful in monitoring the purification of specific antigens from whole tumor cell extracts.