Abstract:Peritoneal cells from BALB/c mice were seeded into 50-mm plastic Petri dishes and exposed either to antigen extracts prepared from individual BALB/c sarcomas having unique tumor-specific antigens, to similar extracts prepared from 14- to 18-day-old mouse embryos, or to culture medium only. Lymphoid cells from BALB/c lymph nodes were than added to the peritoneal cells. Following 4-5 days of co-cultivation, the lymphoid cells were harvested and tested in a 30 h microcytotoxicity assay for reactivity against tumo… Show more
“…Earlier reports from this and other laboratories (Gorczynski, 1976a;Baldwin et al, 1974;Hellstrom and Hellstrom, 1976) The data of Table I (the pooled results from 5 independent experiments) show the cytotoxicity of spleen lymphocytes, prepared from animals at different stages of in vrio sensitization to embryonic antigen, to embryo fibroblasts prepared from different ages of embryo. As already reported, freshly prepared virgin lymphocytes showed negligible cytoxicity to the fibroblast targets, and the same was true for lymphocytes prepared from animals at long times after tumour resection.…”
Section: Resultsmentioning
confidence: 69%
“…4) that the precursor cells for cytotoxic cells underwent size transitions after embryonic antigen challenge/removal in a manner reminiscent of that seen with lymphocytes from animals primed with cells differing at the MHC (see MacDonald et al, 1974;Hayry and Anderson, 1975;Hollander et al, 1974). Furthermore, both tumour bearer/pregnant animals and animals early after removal of in vivo antigen challenge were found to contain a population of cells with peak sedimentation velocity (4 5-7 0 mm/h) which could preferentially inhibit a response to embryoassociated determinants (relative to the response to allo-antigen determinants)-see Table II.…”
Section: Discussionmentioning
confidence: 99%
“…In an auxiliary test of the similarity of the findings in tumour-related and pregnant mice, we have examined the specificity of cytotoxicity to fibroblast targets of lymphocytes from tumour-resected animals re-stimulated in culture with either Comparison of these data with those of Figs (Hayry and Anderson, 1975;Hollander, Ginsburg and Feldman, 1974;MacDonald, Cerottini and Brunner, 1974). The data collected from such studies have led to the concept of alternate cycles of blastogenesis (and development of cytotoxic potential) followed by quiescence (and a return to inactive small cells).…”
Section: Specificity Of Re-stimulation Of Embryoprimed Cells In Tissumentioning
Summary.-The in vitro cytotoxic immune response of spleen lymphocytes from primiparous and tumour-related mice to embryonic cells from embryos of varying age and tumour cells has been investigated. The results indicate that lymphocytes from both primiparous and tumour-related (i.e., tumour-bearing or tumour-excised) animals give a response which is greater than that from cells from control mice ("virgin cells"). Moreover, in this putative anamnestic response the immune cells detect antigenic differences in the cell populations of embryos of varying age, which are not as readily demonstrable when cytotoxicity is derived from virgin cells. As a further indication of the in vivo priming to embryo-associated antigens, the data show that the precursors of cytotoxic cells apparently undergo a blastogenic response in the presence of embryo antigen, and revert to small quiescent cells when antigen is removed, in a way entirely analogous to that described for reactivity of mixed leucocyte cultures to antigens of the major histocompatibility complex. Finally, it seems that in animals immediately after removal of embryonic antigen (and to a lesser degree in virgin or late-embryo-immune mice) there exists a suppressor cell population which inhibits an anti -embryo cytotoxic response far more than an antiallograft response.
“…Earlier reports from this and other laboratories (Gorczynski, 1976a;Baldwin et al, 1974;Hellstrom and Hellstrom, 1976) The data of Table I (the pooled results from 5 independent experiments) show the cytotoxicity of spleen lymphocytes, prepared from animals at different stages of in vrio sensitization to embryonic antigen, to embryo fibroblasts prepared from different ages of embryo. As already reported, freshly prepared virgin lymphocytes showed negligible cytoxicity to the fibroblast targets, and the same was true for lymphocytes prepared from animals at long times after tumour resection.…”
Section: Resultsmentioning
confidence: 69%
“…4) that the precursor cells for cytotoxic cells underwent size transitions after embryonic antigen challenge/removal in a manner reminiscent of that seen with lymphocytes from animals primed with cells differing at the MHC (see MacDonald et al, 1974;Hayry and Anderson, 1975;Hollander et al, 1974). Furthermore, both tumour bearer/pregnant animals and animals early after removal of in vivo antigen challenge were found to contain a population of cells with peak sedimentation velocity (4 5-7 0 mm/h) which could preferentially inhibit a response to embryoassociated determinants (relative to the response to allo-antigen determinants)-see Table II.…”
Section: Discussionmentioning
confidence: 99%
“…In an auxiliary test of the similarity of the findings in tumour-related and pregnant mice, we have examined the specificity of cytotoxicity to fibroblast targets of lymphocytes from tumour-resected animals re-stimulated in culture with either Comparison of these data with those of Figs (Hayry and Anderson, 1975;Hollander, Ginsburg and Feldman, 1974;MacDonald, Cerottini and Brunner, 1974). The data collected from such studies have led to the concept of alternate cycles of blastogenesis (and development of cytotoxic potential) followed by quiescence (and a return to inactive small cells).…”
Section: Specificity Of Re-stimulation Of Embryoprimed Cells In Tissumentioning
Summary.-The in vitro cytotoxic immune response of spleen lymphocytes from primiparous and tumour-related mice to embryonic cells from embryos of varying age and tumour cells has been investigated. The results indicate that lymphocytes from both primiparous and tumour-related (i.e., tumour-bearing or tumour-excised) animals give a response which is greater than that from cells from control mice ("virgin cells"). Moreover, in this putative anamnestic response the immune cells detect antigenic differences in the cell populations of embryos of varying age, which are not as readily demonstrable when cytotoxicity is derived from virgin cells. As a further indication of the in vivo priming to embryo-associated antigens, the data show that the precursors of cytotoxic cells apparently undergo a blastogenic response in the presence of embryo antigen, and revert to small quiescent cells when antigen is removed, in a way entirely analogous to that described for reactivity of mixed leucocyte cultures to antigens of the major histocompatibility complex. Finally, it seems that in animals immediately after removal of embryonic antigen (and to a lesser degree in virgin or late-embryo-immune mice) there exists a suppressor cell population which inhibits an anti -embryo cytotoxic response far more than an antiallograft response.
“…Another role of the LA1 test may be for assessing the activity of fractions obtained during tumor antigen purification, as well as for the screening of various tumor (or embryo) extracts for antigenic activity. Using the assay for the latter purpose, tumor antigen preparations have already been selected, which when added to peritoneal cells and syngeneic lymphocytes from non-immune donors could specifically sensitize the lymphocytes in vitro to the respective tumors used as antigen sources (Hellstrom and Hellstrom, 1976). Similar antigens have also been coupled to chicken erythrocytes, which could subsequently serve as targets in tests for lymphocyte-dependent antibodies (Pollack et al, unpublished findings).…”
A modification of the leukocyte adherence inhibition (LAI) assay of Halliday was used to search for immune reactions against tumor-associated antigens of mouse tumors as well as against embryonic antigens in such neoplasms. Soluble antigen extracts were prepared from transplanted (BALB/c) methylcholanthrene-induced sarcomas and carcinomas, from normal BALB/c embryos taken at 14-18 days' gestation and from kidneys and livers of adult BALB/c mice. Peritoneal cells (PC) from mice immunized against syngeneic tumors gave leukocyte adherence inhibition more commonly when exposed to antigens prepared from the same tumor than did PC from normal (untreated) mice or from mice immunized against a different tumor. However, different tumor antigen preparations varied vastly in their ability to give specific adherence inhibition; some preparations consistently gave a high tumor-specific inhibition, while others did not. This may explain why the degree of reactivity observed was low and its tumor specificity not absolute when data obtained with all different antigen extracts were pooled. PC from multiparous mice gave adherence inhibition when exposed to antigenic extracts from syngenic mouse embryos or from tumors, as compared to PC from virgin mice exposed to the same extracts. Furthermore, PC from tumor-immunized mice reacted more commonly against antigen extracts from mouse embryos than did peritoneal cells from normal untreated mice. Adherence inhibition was not observed when PC from tumor-immunized or multiparous mice were exposed to antigen extracts from adult syngeneic livers or kidneys.
“…Rejection in vivo is mediated by mononuclear cells and specificity for tumor is conferred by T-lymphocytes [3,12]. Lymphocytes sensitized to syngeneic tumor in vitro can effectively produce regression and cure of certain advanced murine tumors [4,18,31,38,40]. In addition to antigen-specific T-lymphocytes, natural killer (NK) cells [21] and other nonspecific cytotoxic cells [27,34] have been suggested to play a role in reducing tumor in vivo.…”
A trial of adoptive immunotherapy was performed in which long-term cultured, interleukin-2 (IL2)-dependent T-lymphocytes were administered to patients with metastatic adenocarcinoma of the lung. Lymphocytes were isolated from explants of cancer tissues that were cultured in medium with recombinant IL-2. These T-cells expressed surface markers of activation, and killed a broad panel of tumor targets. Intravenously injected 111indium-labeled T-cell blasts distributed primarily to lungs, liver, and spleen. Despite a paucity of infused lymphocytes detected by external imaging at sites of tumor, five of seven patients showed reduction of their cancers. However, in no case was greater than 50% reduction of total tumor burden achieved. Evidence of increased delayed cutaneous hypersensitivity to protein antigens was observed in three patients following therapy. We conclude that long-term cultured tumor-derived T-cells can be transferred safely into humans and that these cells may be capable of enhancing immune responses and mediating tumor reduction in vivo.
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