Suppressive Effect of Immunization with Mouse Fetal Antigens on Growth of Cells Infected with Rauscher Leukemia Virus and on Plasma-Cell Tumors

Abstract

The recovery of spleen cells infected with Rauscher leukemia virus (RLV) and grown in Millipore diffusion chambers, the development of RLV-induced splenomegaly, and the cumulative mortality from a transplanted ascites plasma-cell tumor were all suppressed in young adult BALB/c male mice previously primed at 3-weekly intervals with x-irradiated, syngeneic Numerous reports have suggested that fetal cells have antigens that cross-react with specific transplantation antigens in tumor cells (1-6). Although the overall concept is unclear, it is proposed that, upon neoplastic transformation, cells of mature individuals express activity of gene groups that were functional during fetal life but were later repressed. Thus it is possible that during the process of oncogenesis there is a derepression of fetal genes, resulting in the de novo synthesis of antigenic substances detectable as transplantation antigens of tumors. In humans, three classes of embryonal antigens of tumor cells have been described. Gold and Freeman (7) found that fetal gut, liver, and pancreas possess antigen that cross-reacts with specific tumor antigen of the digestive system. These components were named "carcinoembryonic" antigens of the human colon tumor. Abelev (8) mid-gestation, x-irradiated, syngeneic or xenogenic mouse fetus possessed cytostatic antibody to SV40 tumors and were immune to SV40 tumor transplant. Subsequent studies showed that unirradiated fetal cells were poorly immunogenic, differentiated rapidly, and produced embryomas at the site of inoculation (11). Cytotoxic alloantibody against mouse ova was also active against SV40 tumor cells, and immunofluorescence studies revealed that methylcholanthrene-induced

Effect of anti‐embryo immunization on methylcholanthrene‐induced sarcoma growth in BALB/c mice

“…In our experiments a strain-dependent sensitivity to anti-embryo immunization might have interfered as indicated by Ting et al (1973~) who were able to induce an anti-embryo immunity in C57BL and C3H but not in BALB/c mice. I t has been shown, however, that antiembryo immunity can he effectively evoked in BALB/c mice (Hanna et al, 1971 ;Salinas et al, 1972). The difficulty of obtaining anti-embryo antibodies in the BALB/c strain reported by Ting et al (1973~) may be ascribed to the use of embryos taken from non-primiparous females, since primiparous animals seem to provide embryos with the highest immunogenic properties (Coggin et ul., 1971;Girardi et al, 1973).…”

“…It has been shown by several authors that cells of tumors induced by viruses may share antigens with embryos (Pearson and Freeman, 1968;Coggin et al, 1970;Hanna et al, 1971; Ting et al, 1972). While this has been established by using in vitro techniques (Pearson and Freeman, 1968;Ting et al, 1972;Berman, 1972;Girardi et al, 1973); in vivo transplantation methods have yielded conflicting results (Ting, 1968;Coggin et al, 1971 ;Ting et al, 1972;Ting et al, 19736).…”

Response of tumour-related and normal lymphocytes to antigens on fibroblasts from embryos of varying age

“…A number of groups have reported that immunization with foetal tissue is ineffective as a means of inducing tumour-immunity (Pearson and Freeman, 1968;Ting, 1968;Basombrio and Prehn, 1972). In contrast to this, several workers, using SV40-induced tumours (Coggin, Ambrose and Anderson, 1970) and Rauscher-leukaemia-virus-induced tumours (Hanna, Tennant and Coggin, 1971) have suggested that foetal immunization can confer tumour immunity. Perhaps even more striking are the examples where foetal immunization has been shown to enhance the growth of tumours expressing embryo-associated antigens (Castro et al, 1973;Parmiani and Lembo, 1974).…”

Expression by human fetal organs of organ-specific cancer neoantigens as measured by leukocyte adherence inhibition

“…The contribution of these tumor-associated fetal antigens in eliciting effective antitumor immune responses is controversial. In the past, deliberate fetal immunization has had no effect [5,44,66], a protective effect [12,26,46,52] or even a stimulating effect [8,42] on syngenic tumor cell growth. Recent studies have suggested that tumor-associated fetal antigens on fetal cells are immunoprotective [24,27] and can induce a T cell response in vivo against even weakly antigenic metastatic tumors [18].…”