Radioimmune diagnosis of ovarian carcinoma using tumor-associated monoclonal antibodies

GYNECOLOGIC

ONCOLOGY

15,

134-144 (1983)

Abstracts of Papers Presented at the February 1983 Meeting of the Society of Gynecologic Oncologists Scottsdale, 1. Rudioimmune JOHN W.

H. F.

Arizona, February 6-9, 1983

Diagnosis qf Ovariun Carcinoma Using Tumor-Associated A. A. EPENETOS. K. E. BRITTON, B. G. WARD,

SHEPHERD,

Monoclonal MARIA

Antibodies.

GRANOWSKA.

AND

BODMER.

Mouse monoclonal antibodies HMFG I and HMFG 2 directed against a component of human milk fat globule membranes react strongly with the lactating breast and also a wide spectrum of epithelial neoplasms. This applies particularly to ovarian adenocarcinoma, whereas the antibodies only react weakly with normal resting breast and other epithelial tissues. They are therefore not tumor but epithelial specific and because of increased reactivity with adenocarcinomas, may be considered tumor associated antibodies. These antibodies were administered to immunodeficient mice bearing human ovarian cancer xenografts. Radioscans at various time intervals demonstrated the presence of tumor in all the mice. A clinical study was undertaken using “‘I-labeled monoclonal antibodies in 20 patients with ovarian cancer. Tumors became visible at times ranging from 3 min to 24 hr after injection. Detection was achieved in all patients with tumor uptake of, on average, 0.6% of the labeled antibody. Exploratory laparotomy was performed following the scan. Confirmation of antibody in the tumors was by audioradiography and immunoperoxidase staining of surgically removed tissues. This technique complements existing investigatory methods and raises the possibility of achieving earlier diagnosis in otherwise undetectable disease. Targeting of monoclonal antibodies to ovarian cancer in vivo provides a basis for selective therapy in oncology.

2. Monoclonal Antibody Recognition qf [‘HJMonohydroxytamoxijen-Receptor Receptor Complex in Ovarian Epithelial Carcinoma. J. A. HOLT, M. A. L. HERBST, A. TATE, AND V. C. JORDAN.

nnd ““I-EstrudiolMAKII,

G.

L.

GREENE,

Previously we demonstrated estrogen receptor (>500 fmoleig wet wt) in 40-60% of primary and metastatic ovarian epithelial carcinomas. We have now used a monoclonal antibody (D-547 SPF) against human breast cancer estrogen receptor to investigate whether ovarian carcinoma estrogen receptor has the potential to bind antiestrogens and radiohalogenated estradiol. DES-inhibitable [‘Hlmonohydroxytamoxifen and “I-estradiol binds to cytosol estrogen receptor in the 8 S region upon sedimentation velocity analysis thru low salt linear sucrose gradients in the ultracentrifuge. The 8 S bound moiety was confirmed to be receptor by the use of high salt (0.5 M KCI) gradients that caused its shift to the S S region; monoclonal antibody against human breast cancer estrogen receptor shifted the 5 S binding peaks to the 9 S region indicating antibody recognition and complex formation with the receptor carrying the radiolabeled ligands. The estrogen specificity of the antibodybound receptor was verified by the fact that IOO-fold excess molar DES but not testosterone or progesterone inhibited its [‘Hlmonohydroxytamoxifen and “‘I-estradiol binding. We conclude that estrogen receptor in primary as well as metastatic ovarian epithelial carcinoma is (I) antigenically similar to human breast cancer estrogen receptor and (2) that it can bind biologically active antiestrogen and radiohalogenated estrogens. The latter suggests a potential use for tumor management. 134 0090-82581831010134-1 I$01 SO/O Copyright All rights

0 1983 by Academic Press, Inc. of reproduction in any form reserved.