[An attempt of determining anti-tumour antibodies in neoplasms of the mammary gland (author's transl)].
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Antibodies, Neoplasm↗
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Investigations for skin antibodies in malignant neoplasms.
A group of 451 patients with various malignant neoplasms was investigated for the presence of antibodies against the intercellular substance in epidermis and against the basement membrane in the skin, using the immunofluorescence method. None of the patients had bullous disease. Circulating basement membrane antibodies were found in a 63-year-old man with lung cancer. None of the patients had antibodies against the intercellular substance. No in vivo bound intercellular or basement membrane antibodies were found.
Antibodies, Neoplasm↗
Humoral reactions in syngeneic hosts against tumor cell surface incomplete saccharide moieties.
Components on the surface of MM2 ascites mammary carcinoma cells induce agglutination factors in the serum of syngeneic host C3H/He mice, and bind the factors in vitro. These components have been classified into three groups: MM2-specific substances, mammary tumor virus (MTV)-associated substances and tumor-associated embryonic materials. The substances contained saccharide moieties and their terminal sugar residues were essential for the binding of the serum factors. These terminal saccharides were exposed during cell proliferation,but masked in stationary cells, at least partly, due to elongation of the saccahride moieits. The terminal structures of these polysaccharide moities of growing and stationary cells were studied by semiquantitative tumor cell agglutination using the agglutinating activities against MM2 cells of MM2-regressor serum and of FMA/R- and Ehrlich-regressor sera which had partial cross-agglutination activities. Agglutination by phytohemagglutinins, inhibition of the agglutination by saccharides or with isolated cell surface components and treatment of the cells with glycosidases were also used for this purpose.
Agglutination↗
Endogenous immune complex nephropathy associated with malignancy I. Studies on the nature and immunopathogenic significance of glomerular bound antigen and antibody, isolation and characterization of tumor specific antigen and antibody and circulating immune complexes.
Three patients with clear cell renal carcinoma and one with another intrarenal malignancy were studied for the presence of glomerular localized immunoglobulins, complement components and tumor specific antigen and antibody by immunofluorescence. To determine the association and elucidate the pathogenic mechanisms involved in the relationship between tumors and glomerular deposits, antibody eluted from tumor tissue and renal glomeruli, cryoproteins, serum antibodies and rabbit antisera to tumor tissue were tested for specificity to antigen. The relationship between tumor antigens and the lipoprotein antigen localized in normal proximal tubular brush border (RTE) and the small bowel mucosa, was studied by immunofluorescence, absorption and blocking studies as well as complement fixation. Immunoglobulins and complement components were localized in the glomeruli and tumor membrane of all patients. Sera and glomerular fixed antibody from three patients with renal cell carcinoma localized to normal proximal tubular brush border and jejunal mucosa as well as to tumor membrane and the glomeruli and proximal tubules of all of these three patients. Anti RTE activity was also detected by complement fixation. Immunologic similarity between RTE and renal cell carcinoma antigen was confirmed by absorption studies. Furthermore, cryoprecipitable complexes of tumor antigen and specific antibody were isolated from the serum. The tumor antibody was immunologically similar to RTE. In the other case the rabbit anti-tumor antibody and the patient's serum fixed to the tumor membrane and kidney of the patient but did not show cross reactivity with the renal cell carcinoma or RTE. These studies suggest that the tumor antigen in renal cell carcinoma is similar to RTE and the glomerular deposits represent tumor antigen and antibody complexes. In addition these investigations support the hypothesis that tumor immune complexes are significant in the glomerular lesions, and that the origin of renal cell carcinoma is in the proximal tubule. The investigations also show that tumor antibodies are specific for tumors of the same morphological type but not for other tumors in the same tissue. Moreover, the renal glomerulus appears to be a chosen anatomic site for deposition of tumor antigens and antibodies and studies of the kidney may provide insight into the nature of tumor antigens and antibodies. Cryoprecipitation appears to be a valuable method in isolation of tumor complexes and characterization of tumor specific antigen and antibody.
Absorption↗
Analysis and reversal of the inhibition of cytophilic antibody receptors produced by antibody.
Administration of hyperimmune antibody to leukemia L1210 to allogeneic mice inhibited the development of macrophage-mediated immunity to L1210 in those hosts. In contrast to immunized mice, animals pretreated with antibody showed rapid activation of their peritoneal macrophages, followed by their disappearance and the inability of the residual peritoneal monocytic cells to attach L1210 cells even in the presence of proved cytophilic antibody to L1210. The inhibitory activity of the antibody, which resided entirely in its IgG2 fraction, was manifested only when the specific antigen (L1210 cells) was also injected within 2 days. Pretreatment with antibody to a different leukemia, EL4, failed to inhibit the monocytic uptake of L1210, but it did inhibit uptake of EL4 by monocytes if injected with its homologous antigen. Restoration of the functional capacity of macrophages was accomplished by injecting 1 X 10-7 bone marrow cells i.v. into "suppressed" mice, but 1.5 X 10-7 thymocytes failed to correct the defect. Significantly, thymocytes antagonized the restorative capability of bone marrow cells when they were injected concomitantly. These results indicate that specific inhibition of cytophilic antibody receptors on monocytes could be accomplished through a direct mechanism involving activation and exhaustion of macrophages and an indirect mechanism, perhaps mediated through "suppressor" thymus-derived cells. Although enhancement of the growth of leukemia cells did not occur, several parallels exist in mice with enhanced growth of different tumors. This inhibiotry phenomenon may thus represent another instance of "blocking" in tumor immunity, where the target of suppressive antibody-antigen is the macrophage as well as the lymphocyte.
Animals↗
Immune function at diagnosis in relation to responses to therapy in acute lymphocytic leukemia of childhood.
Tests of immune capacity were performed on blood from 49 children with newly diagnosed, untreated acute lymphocytic leukemia, and relation to prognosis was determined. Patients were treated with multiple-drug therapy and prophylactic cranial irradiation. Median follow-up time was 16 mo (range 10--37 mo). Principal unfavorable findings at diagnosis were absolute numbers of T lymphoid cells outside the range 850--2500/mul blood, absence of whole blood responses to phytohemagglutinin in vitro, a low titer of complexed antibody, and the presence in serum of free leukemic blast cell membrane antigen. Fourteen patients showed two or more unfavorable findings at diagnosis. Eleven of these have died. Four of the remaining 35 patients have died. A shorter duration of first remission was found among patients with abnormal numbers of T cells at diagnosis. The findings suggest that the immunologic capacity of the patient at diagnosis is an important determinant in responses to therapy.
Adolescent↗
Evidence for common and distinct determinants of colon carcinoembryonic antigen, colon carcinoma antigen-III, and molecules with carcinoembryonic antigen activity isolated from breast and ovarian cancer.
This study was designed to answer the question, do molecules with carcinoembryonic antigen (CEA) activity from colon, breast, and ovarian cancer differ? Extracts of two breast and three ovarian cancers with CEA activity were compared to three colon cancer CEA preparations and to the related antigen, colon carcinoma antigen-III, in terms of lectin- and antiserum-binding properties. With the use of Farr-type radioimmunoassays with the lectins, concanavalin A and wheat germ agglutinin, the iodinated colon CEA and CEA-like preparations from breast and ovarian cancer all showed distinctly different patterns of binding. Specificity of binding was confirmed by inhibition studies with the relevant monosaccharides. Similarly, with antisera prepared against colon CEA, colon carcinoma antigen-III, or breast CEA, it was shown that, although all preparations shared some antigens, unique antigenic determinants were also present on all preparations. These data are consistent with the concept of a series of closely related CEA and CEA-like molecules with distinct characteristics for each tissue source of CEA.
Antibodies, Neoplasm↗
Detection of antibodies to embryonic antigens in sera of multiparous or colon tumor-bearing rats by a new indirect immunofluorescence assay.
An indirect immunofluorescence assay using antigen coupled to agarose beads detected high titers of antibody to embryonic antigens in sera from multiparous rats and rats bearing colon carcinomas. Sera from pregnant rats had antibody titers greater than 10(3) and some rats still had titers greater than 10(2) 30 weeks after the end of pregnancy. Rats which developed colon carcinomas after treatment with 1,2-dimethylhydrazine were bled monthly between the end of treatment and detection of carcinoma. Antibody to embryonic antigens appeared in their sera at least 2 months before roentgenologic diagnosis of tumor.
Animals↗
Polyclonal natural antitumor antibody binding dynamics: preferential release of surface membrane molecules and increased metastasis.
Flow cytometry revealed the dynamic nature of polyclonal whole serum naturally occurring IgG and IgM antibody binding to the syngeneic murine T cell lymphomas SL2-5, L5178Y-F9 and the in vitro selected high natural antibody binding variant L5178Y-F9 TPA/NAb+3. This was particularly evident at physiological conditions where the temperature was 37 degrees C and the concentration of reactive serum natural antibodies (NAb) was high. Lower binding was observed at 37 versus 4 degrees C, or after raising the temperature from 4 to 37 degrees C, a procedure which was associated with an augmented loss of 125I-surface-labelled material from cells incubated in NAb compared to cells exposed to growth media. Even at 4 degrees C, NAb binding exhibited biphasic kinetics suggesting a loss of surface-bound NAb and a subsequent cycle of NAb uptake. The increased intravenous liver metastasis potential of the high NAb binding L5178Y-F9 TPA/NAb+3 corresponded with its higher total loss of 125I-surface-labelled material when incubated in NAb at 37 degrees C, and with its extensive loss of NAb binding when the temperature was raised from 4 to 37 degrees C. These observations are consistent with the idea that molecules released from the cell may contribute to the higher metastasis. This thinking was supported by the increased metastasis of tumor cells injected intravenously, either with serum in which they had been preincubated at 37 degrees C or into mice treated with supernatants from tumor cells incubated in NAb.
Animals↗
Correlations between humoral immunity and successful chemotherapy-immunotherapy.
Experiments were designed to evaluate the characteristics of the humoral immune response induced by active immunotherapy, both specific (neuraminidase-treated tumore cells) and nonspecific (Bacillus Calmette-Guérin organisms), in the L1210-C57BL/6 X DBA/2F tumor-host system. Tumor burden was minimized with chemotherapy (1,3-bis-(2-chloroethyl)-1-nitrosourea) prior to immunotherapy. A marked increase in the concentration of serum immunoglobulins (immunoglobulin M, immunoglobulin G, and immunoglobulin G) was observed following successful therapy. The highest concentration of these immunoglobulins was found in mice given both Vibrio cholerae neuraminidase-treated cells and B. Calmette-Guérin after chemotheraphy. Tumor-specific immunoglobulin M and immunoglobulin G, as measured by indirect immunofluorescnece, were detected in the sera during the course of successful therapy. Positive immunofluorescence was not observed with progressive sera. Complement-dependent cytotoxic activity against L1210 cells was first detected 5 days after immunotherapy, and increased for several weeks. A high level of cytotoxic activity correlated with successful therapy, whereas low levels were foun in treated mice with recurring tumors. Serum cytotoxicity was not detected in untreated mice with progressively growing tumor.
Animals↗
Studies on specific humoral immunity in leukemia.
The paper concerns some results in studies on humoral immunity in human and animal leukemia obtained in author's laboratory (1970-1974). The data presented here disclose immunological mechanisms of mice viral leukemogenesis (cytotoxic and blocking antibodies interrelations). The existence of specific humoral immune response in acute leukemia patients was established (immunoglobulins with the properties of antibodies were revealed in 42.6% of patients). Different forms of specific humoral immunity manifestations in different types of leukemia were distinguished (areactive, nonspecific, cytotoxic, blocking and mixed forms.
Animals↗
Immunofluorescent studies on chimpanzee humoral responses to human melanoma cells.
Eight chimpanzees were immunized, each with a single melanoma cell line. It was found that the serum of only one of the eight chimpanzees showed immunofluorescence with four of the five melanoma cell lines at the membrane surface; but it showed no fluorescence with normal skin fibroblasts, WI-38 cells, HeLa cells, human or monkey kidney cells. With appropriate absorption studies it was found that the antiserum was specific to melanoma cell lines. Trypsinated cells showed bright patchy membrane fluorescence, whereas non-trypsinated cells showed bright full ring fluorescence. The chimpanzee's antibody was C'-fixing IgG. It was concluded that the immunized chimpanzee produced antibody to surface antigen(s) common to four of the five melanoma cell lines tested.
Animals↗
Surface antigenic characteristics of human glial brain tumor cells.
The surface antigenic characteristics of human glial brain tumor (HGBT) cells were studied by complement-dependent cytotoxic antibody assays and indirect membrane immunofluorescence. Eight permanent, well-characterized cell lines derived from human gliomas were used for analysis with antisera raised by hyperimmunization of nonhuman primates (Macaca fascicularis) with glioblastoma multiforme tissue or established HGBT cells lines. Exhaustive absorption of these antisera to remove predominantly antispecies activity rendered HLA nonreactive "preabsorbed" antisera, which reacted with a large panel of gliomatous and nongliomatous human tumor cells; 1 carcinoma, 2 sarcomas, 2 melanomas, 1 neuroblastoma, and 8 HGBT cell lines. Four lymphoblastoid lines and 2 carcinomas were unreactive. After further absorption with a human osteogenic sarcoma cell line, the antisera demonstrated significant levels of reactivity for 8 tested HGBT cell lines and no longer reacted with the nongliomatous cultured tumor cells lines. Therefore, extensive absorption of nonhuman primate anti-human glioma sera removed all activity for the nongliomatous cell lines tested, but it left significant reactivity against a glial tumor cell line-associated antigen(s) present on all 8 human glioma cell lines tested.
Antibodies, Neoplasm↗
Biological properties of myeloma proteins.
The paraproteins frequently cause major symptoms in patients with plasma cell dyscrasias. This may be due to their quantity in the circulation, to some unusual physicochemical property, or to a biological effect resulting in interaction with other serum proteins. Detection of antibody-combining activity in myeloma proteins has led to important new information on combining-site structure and the kinetics of antigen-antibody-combining activity. Some antibody-combining specificities seem to be present in a higher than expected frequency. As yet, no major therapeutic advances have followed this more precise characterization of the paraprotein, though some interesting possibilities have been explored in animal models.
Amino Acid Sequence↗
Ductular carcinoma of the breast: serum antibodies to tumor-associated antigens.
Serum antibodies to tumor-associated antigens of breast carcinoma have been studied by indirect immunofluorescence in 109 patients with breast carcinoma and 125 controls, including age/sex matched normal individuals, patients with nonmalignant disease, and patients with malignant disease other than breast cancer. We report here that sera of a large proportion of patients with ductular carcinoma of the breast have antibodies to cell surface and/or intracellular antigens of autologous tumor cells and include evidence that the antigens are absent from a considerable range of normal and other types of malignant tissues. In addition to testing of control sera, specificity of the reacting antibodies was investigated further by testing of sera with normal breast tissue and the absorption of sera from breast cancer patients with various normal tissues and cancer cells. The significance of the findings in breast cancer is discussed.
Antibodies, Neoplasm↗
Specific antigen of murine erythroblasts.
A new antigan has been revealed by means of antisera against Rauscher virus in mice with Rauscher virus-induced leukemia. This antigen appears to be different from both Rauscher type-specific antigen and MULV-gs-1 (p-30), as shown by studies of electrophoretic mobility and immunochemical specificity. Except in leukemic mice it was also found in low levels in both serum and spleen extracts of healthy mice of a number of strains. Furthermore, this antigen was regularly demonstrated by immunofluorescence on the surface of erythroblasts, but not on the surface of erythrocytes, lymphocytes, polymorphonuclear cells and thymocytes, and was shown to be different from fetal hemoglobin. Therefore, it is referred to as antigen of erythroblasts (Ag-Eb), which seems to represent a surface marker for a certain differentiation stage of erythroid cells.
Animals↗
Malignant transformation of hamster cells following infection with bovine herpesvirus (infectious bovine rhinotracheitis virus.
Hamster embryo cells, following infection with IBR virus, showed malignant transformation. Hamsters of all ages, inbred or random bred, inoculated with two of the transformed cell lines developed solid tumors. Preliminary characterization of the tumors induced by one of the cell lines has indicated undifferentiated sarcomas. Viral specific antigen was detected in about 5% of the transformed cells and 10% of primary tumor cells in culture. Viral specific antibody was detected in the serum of tumor-bearing hamsters by the indirect immunofluorescent method, but no neutralizing antibodies were found. Infectious virus has not been recovered from either the transformed or tumor cells by cocultivation with bovine embryonic kidney cells.
Animals↗
Tumor-associated antigen in bovine and ovine lymphosarcoma.
Specific tumor-associated antigens were found on the membrane and in the cytoplasm of lymph node cells and peripheral blood lymphocytes (PBL) from cattle and sheep with lymphosarcoma by immunofluorescence tests. Materials from 15 cattle with the adult form of lymphosarcoma were examined. Cytoplasmic antigen was detected in fixed tumor cells from all 15 cases and in PBL from 9 cases tested. Membrane antigen was detected in living cells from 10 of the cases tested. In 3 calf-type cases, cytoplasmic antigen was found in a few (1 to 3%) of the tumor cells, while 1% of the cells from 2 thymic cases had cytoplasmic tumor antigen. In 15 cattle infected with bovine leukemia virus (BLV) but with no evidence of tumor, PBL from 3 cattle had the tumor-associated antigen in the cytoplasm. Negative results were obtained with similar tests done with 9 normal cattle that had no detectable BLV or BLV antibody. Cells from tumors induced with BLV in 5 sheep also had cytoplasmic antigen and membrane tumor-associated antigen. Tumor-associated antigen was found in PBL from 1 or 7 BLV-infected sheep with no clinical evidence of tumor. Similar tests were negative on 4 normal sheep.
Animals↗