44-KD ONCOFETAL TRANSPLANTATION ANTIGEN IN RODENT AND HUMAN FETAL CELLS - IMPLICATIONS OF RECRUDESCENCE IN HUMAN AND RODENT CANCERS

Objective: This article summarizes the phase-specific nature of a cell surface, 44-kd tumor-associated transplantation antigen glycoprotein expressed during early and middle gestation in a portion of rodent and human fetal cells during normal fetal tissue development and illustra tes how this glycoprotein is consistently recrudesced in primary and e stablished human squamous cell carcinomas and other human and rodent t umors. The oncofetal antigen was not detectable in any human or rodent term fetal tissue or normal adult tissues tested. The tumor-associate d transplantation antigen was tumor specific, yet not germ-line specif ic (expressed in lymphomas, sarcomas, and carcinomas) in human or rode nt cancers. Rodent model tumor studies have shown 44-kd oncofetal anti gen can act as a tumor-associated autoantigen of potential use in canc er detection and therapy. Design: The oncofetal antigen was detected b y immunogenicity, flow cytometry, and Western blotting in syngeneic ro dent tumor recipients and by the last two methods in humans with progr essive cancer. Syngeneically derived mouse monoclonal antibody (MoAb 1 15) was used to identify 44-kd oncofetal antigen. Early to middle gest ation, oncofetal antigen-positive, mouse embryo/fetal cells used to, s timulate the hybridoma were tested for immunogenicity as a tumor-assoc iated transplantation antigen in syngeneic hosts. Setting and Patients : Patients presenting with head and neck squamous cell carcinoma (N=25 ) and other carcinomas at the University of South Alabama Medical Cent er, Mobile, underwent a biopsy, and the tumors were mechanically dispe rsed and were then tested for oncofetal antigen expression directly in flow cytometry. The tumors were also cultured and tested as squamous carcinoma cell lines. Growing squamous carcinoma cells and uncultured tumor cells were stained with MoAb 115 or control MoAb. Extracts of th e cells were banded by electrophoresis in gels, Western blotted, and r eacted with MoAbs and enzyme-linked immunosorbent assay second antibod y. Time-mated mouse fetus and human fetal cells were also stained with MoAb 115 or control antibody and analyzed in the flow cytometer. Resu lts: Eight- to 13-day mouse fetal cells conferred protection against s yngeneic tumor challenge. Term 18- to 21-day fetal or neonate or adult mouse cells were nonprotective. All head and neck squamous cell carci nomas tested expressed 44-kd oncofetal antigen by flow cytometric anal ysis and in Western blots as did ATCC cell lines of these tumors, wher eas normal control tissues were negative. Second trimester human fetal cells were 44-kd oncofetal antigen positive. A large spectrum of rode nt sarcomas and lymphomas express the OFA. Conclusions: Shared 44-kd o ncofetal antigen OFA offers promise as a tumor detection marker in hum an squamous cell carcinoma and other human carcinoma development, and syngeneic mouse tumors are good model systems to explore oncofetal ant igen antigenicity.