Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies reactive to line 10 (L10) hepatocarcinoma cells, but not to L2C leukemia cells, of strain 2 guinea pig were produced and characterized. Complement-mediated cytolysis assay and quantitative absorption analysis revealed that one of the monoclonal antibodies, 3C4 antibody (IgG2a), was highly specific for L10. Neither normal guinea pig tissues including adult and fetal liver, nor other hepatomas of strain 2 guinea pig, line 1 (L1) and Hepatoma III, were reactive with the 3C4 antibody. Another antibody, 2E4 (IgM), was reactive to the liver, kidney and spleen cells but not to the thymocytes, lymph node cells, brain and red blood cells of the guinea pig. The 2E4 antibody reacted to Hepatoma III but not to L1 cells. Therefore, 3C4 antibody is specific to a tumor-associated antigen of L10 hepatoma, and 2E4 antibody is cross-reactive with a certain differentiation antigen of normal tissues. The 3C4 antibody showed antibody-dependent cytotoxicity. Since 3C4 antibody was different in the isotype and the antigen recognized from a monoclonal antibody (D3) which was reported from the NIH in the USA, 3C4 is a new monoclonal antibody reactive with L10 hepatocarcinoma.
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PMID:New monoclonal antibodies specific for the guinea pig line 10 hepatocarcinoma. 311 52

The specificity of CTL generated against tumors induced by murine leukemia viruses (MuLV) has been reported to parallel the expression of two serologically defined tumor cell surface antigens--the cross-reactive FMR antigen expressed on the surface of tumors induced by Friend, Moloney, and Rauscher MuLV, and the Gross cell surface antigen (GCSA) expressed on tumors induced by AKV/Gross MuLV. We examined the specificity of CTL generated against MuLV-induced tumors and identified two distinct patterns of reactivity. The first follows the traditional pattern of FMR vs GCSA reactivity as assessed on a panel of established MuLV-induced lymphomas. However, CTL exhibiting this pattern of reactivity are incapable of lysing MuLV-infected fibroblasts. CTL exhibiting the second pattern of reactivity are capable of lysing MuLV-induced lymphomas as well as MuLV-infected fibroblasts. In addition, these CTL exhibit extensive cross-reactivity between lymphomas and fibroblasts infected by both groups of MuLV. Our results suggest that CTL exhibiting the traditional FMR vs GCSA pattern of reactivity are directed against a tumor-associated antigen and not against virus-encoded antigens, and that CTL directed against MuLV-encoded antigens demonstrate extensive cross-reactivity, including the ability to lyse AKV-infected cells.
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PMID:The immune response to Moloney murine leukemia virus-induced tumors: induction of cytolytic T lymphocytes specific for both viral and tumor-associated antigens. 349 Nov 52

A panel of murine monoclonal antibodies (MAbs) was produced by fusing NS-0 myeloma cells with spleen cells of a BALB/c X DBA/2 F1 mouse hyperimmunized against a highly immunogenic subline of the L1210 leukemia obtained by in vivo treatment of the L1210 parental line with the antitumor drug 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC). Among the 52 MAbs produced 16 (anti-D) were specifically cytotoxic in a complement-dependent cytotoxicity assay for the drug-altered subline and the others (anti-L) also cross-reacted with the L1210 parental leukemia. Six anti-D and three anti-L MAbs were selected for detailed studies of tissue specificity. In quantitative absorption experiments the antigens defined by these antibodies could not be detected on cells from normal mouse tissues (lung, liver, kidney, heart, spleen, and thymus). The reactivities of both anti-D and anti-L MAbs against a panel of L1210/DTIC sublines obtained at different times were assayed. The results showed that the antigenic specificities defined by anti-L MAbs were expressed on almost every L1210/DTIC subline while the anti-D MAbs detected antigenic structures specific for the L1210/DTIC used for the immunization. None of the MAbs tested cross-reacted with the L5178Y lymphoma or with its DTIC-altered sublines. The failure of anti-D MAbs to cross-react with cells from other L1210/DTIC sublines supports the hypothesis that the immunological alterations induced by the DTIC treatment are the consequence of mutagenic activity of the drug. On the other hand the presence of anti-L antigens on the cells of every L1210 subline indicates that the DTIC alteration is not accompanied by a loss of the tumor-associated antigen from the L1210 leukemia.
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PMID:Monoclonal antibodies to the L1210 murine leukemia cell line and to a drug-altered subline. 405 6

We have attempted to identify the antigen on L5178Y cells that is the target for peritoneal cytotoxic T-lymphocytes (CTL) generated in L5178Y-O (original) immunized and challenged DBA/2 mice during establishment of the L5178Y cell tumor dormant state. These CTL exhibited in vitro lytic activity against methylcholanthrene-induced L5178Y and P815Y cells as well as Gross virus-induced BALB/c cells but not against a variety of other H-2d-tumor cell lines. The pattern of susceptibility to cell-mediated immune cytolysis was identical to the pattern of AB-dependent complement-mediated cytolysis produced by a rabbit anti-L5178Y antiserum. Quantitative expression of surface H-2d determinants was not a limiting factor in tumor cell lysis by CTL. The degree of CTL lysis of the susceptible cell lines was directly related to the amount of tumor-associated antigen expressed on the cell surface. The pattern of in vitro susceptibility to CTL lysis correlated well with in vivo transplantation resistance. The L5178Y cell antigen target for both CTL and Ra-anti-L5178Y serum lysis is likely to be either an endogenous AKR ecotropic viral glycoprotein with a molecular weight of 71,000 or one of two cell surface determinants, at Mr 85,000 and 135,000. These higher-molecular-weight antigens are neither endogenous AKR ecotropic viral-induced nor murine leukemia virus group-specific precursor structural proteins but may be transformation antigens shared by the susceptible tumor cell lines.
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PMID:Cross-reacting antigens on L5178Y cells which serve as targets for cytotoxic T-lymphocyte lysis during establishment of the tumor dormant state. 617 3

The quantity of receptors expressed by specialized cells for hormones, foreign antigenic substances, and other chemical stimuli diminishes after they associate with ligands, correlating with a specific reduction in the responsiveness of the cell to further stimulation. Ligand-induced adaptation of membrane receptors may be akin to antigenic modulation--the reversible disappearance of membrane-associated determinants stimulated by specific antibodies. Antigenic modulation has been studied extensively in the thymus-leukemia (TL) system of mouse leukemias. Antibody-induced changes in the quantities of TL antigens expressed by ASL-1 and RADA-1 cells, independently arising leukemia cell lines of strain A mice, are outgrowths of their metabolic turnover. After interacting with TL antibodies, the rate of TL antigen disappearance from the membrane increases while the rate of antigen synthesis remains unchanged. Antiserum with specificities for two membrane-associated determinants of ASL-1 cells, TL and a tumor-associated antigen, leads to modulation of TL antigens alone; the tumor antigen persists. Selectivity of modulation is taken as an indication that complex cellular controls govern the affect of antiserum on the expression of membrane antigens. To detect the presence of regulatory controls governing the expression of membrane determinants, stable somatic hybrids of ASL-1 murine leukemia cells and LM(TK)- cells, a sustained mouse cell line, were prepared and antiserum affects on membrane antigen expression were investigated. The metabolic half-lives of each of three antigen determinants investigated was distinct from the others examined. The hybrid cells have lost their capacity to mudulate TL antigens. TL antigens of hybrid cells, unlike those of parental ASL-1 cells, continue to be expressed in the presence of high titers of TL antiserum. Similarities between antigenic modulation and down regulation exist, among which are the fate of receptor-ligand complexes, changes in their metabolism after binding to ligand, and the dependence of the reactions upon continued sources of cellular energy.
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PMID:Adaptation of membrane-associated determinants is an outgrowth of their metabolism. 624 90

The cytotoxic sensitivity of murine leukemia virus (MuLV)-infected and noninfected fibrosarcoma cells in syngeneic inbred WKA/Hok rats was compared by in vitro cell-mediated 51Cr release cytotoxicity assay. A highly significant increase in cytotoxic sensitivity of target cells was observe in MuLV-infected tumor cells as compared with noninfected cells when spleen cells from syngeneic tumor-bearing hosts (TBH) were used as a source of effector lymphocytes. The cytotoxicity of spleen cells against MuLV-infected tumor cells was specifically directed to the tumor-associated antigen (TAA), but not to the virus-associated antigen. However, there was no quantitative difference in the amount of TAA on the cell membranes between virus-infected and noninfected tumor cells as measured by a quantitative absorption test of anti-TAA serum. The cytotoxic activity of spleen cells from TBH against MuLV-infected tumor cells was abrogated by the treatment of anti-T-serum plus complement and significantly decreased after trypsin treatment. Spleen cells from normal rats given injections of immune sera from TBH acquired the cytotoxic activity against MuLV-infected tumor cells.
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PMID:Increased sensitivity of murine leukemia virus-infected tumor cells to lymphocyte-mediated cytotoxicity. 626 45

The expression of tumor-associated antigens on the DBA/2 lymphoma L1210 and three L1210 sublines, each resistant to a different antileukemic agent [guanazole, methylglyoxal-bis(guanylhydrazone), and 4,4-diacetyldiphenylurea-bis(guanylhydrazone)] was investigated by the use of monoclonal hybridoma antibodies. Hybridomas were produced by the fusion of spleen cells from DBA/2 mice immunized with irradiated L1210 or L1210 subline cells and cells of a non-immunoglobulin-secreting BALB/c myeloma variant. Three clones producing antibodies reacting with L1210 or L1210 subline cells were used to study the antigenic expression of L1210 and L1210 subline cells. Monoclonal antibodies from anti-L1210 and anti-L1210 subline hybridomas exhibited a greater reactivity with L1210 subline cells than with L1210 cells in complement-dependent cytotoxicity, quantitative absorption, and membrane immunofluorescence experiments, thereby demonstrating a tumor-associated antigen shared by L1210 and the L1210 sublines and an increased expression of this antigen on subline cells. Cross-blocking tests of antibody binding demonstrated that monoclonal antibodies from anti-L1210 and anti-L1210 subline hybridomas recognized the same or very closely situated antigenic determinants on the tumor cell surface. Most syngeneic and allogeneic tumor cells used as controls failed to react with the anti-L1210 and anti-L1210 subline hybridoma antibodies. However, two syngeneic tumors, L5178Y and P388-D1, demonstrated a significant reaction with the monoclonal antibodies. In addition, several spontaneous mammary tumors from C3H/St and DBA/2Ha, both high-frequency mammary tumor strains, reacted in various degrees with anti-L1210 or anti-L1210 subline hybridoma antibodies in absorption tests and in immunofluorescence experiments. On the other hand, liver, kidney, and spleen from normal C3H/St mice, as well as mammary tumors from BALB/c and C3Hf, both low-frequency mammary tumor strains, did not demonstrate significant reactivity in similar experiments. Normal lactating mammary glands from high-frequency mammary tumor mouse strains reacted with the monoclonal antibodies, whereas lactating mammary glands from low-frequency mammary tumor mouse strains were negative by this method. Purified murine mammary tumor virus preparations reacted strongly with the monoclonal antibodies in solid-phase radioimmunoassays, whereas a purified murine leukemia virus preparation failed to do so in similar experiments. These results indicate that the tumor-associated antigen(s), differentially expressed on L1210 and L1210 subline cells, is related to an antigen which is associated with the murine mammary tumor virus.
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PMID:Differential antigenic expression of the DBA/2 lymphoma L1210 and its sublines: cross-reactivity with C3H mammary tumors as defined by syngeneic monoclonal antibodies. 634 55

Immunization of strain 2 guinea pigs with 10(7) syngeneic Ia+ L2C leukemia cells in adjuvant leads to L2C tumor protection. After subsequent challenges with L2C tumor cells, the sera and spleens of the protected guinea pigs had detectable anti-L2C reactivity. The L2C antibody reactivity was preferentially associated with the IgG1 isotype fraction and bound equally well to Ia+ or Ia- L2C cells but failed to bind to normal guinea pig lymphoid cells or hepatocarcinoma tumor cells. The binding was inhibited appreciably with F(ab')2 fragments specific for the L2C surface IgM idiotypic determinants. By contrast, the same reagent failed to inhibit the specific cytolysis of L2C tumor cells by T lymphocytes present in the spleens of L2C protected guinea pigs. However, the T cell mediated cytolysis was inhibited to some extent by F(ab')2 fragments specific for the B.1 alloantigen on the L2C tumor cells. These results indicate that the specificity of the L2C T effector cells appears to differ from that of the L2C antibodies and that in the elicitation of a humoral response the IgM idiotypic determinants may function as a tumor-associated antigen.
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PMID:Immune response in strain 2 guinea pigs to the syngeneic L2C leukemia. 635 30

In studies of antitumor antibody-cytotoxic agent conjugates as potential antitumor agents with improved tumor specificity, the toxic subunit A-chain of ricin was conjugated with a monoclonal antibody to a tumor-associated antigen expressed weakly on murine leukemia L1210 cells and strongly on L1210/GZL cells, a guanazole-resistant subline of L1210, employing N-succinimidyl 3-(2-pyridyldithio)propionate as cross-linking agent. The conjugate (anti-L1210 conjugate) exhibited a potent concentration-dependent cytotoxicity against cultured L1210/GZL cells, and inhibited cell growth at concentrations over 0.8 micrograms/ml. The conjugate killed all L1210/GZL cells at a concentration of 100 micrograms/ml. Neither nonimmune conjugate similarly prepared from mouse nonimmune IgG nor unconjugated anti-L1210 IgG alone showed cytotoxicity against L1210/GZL cells. When (BALB/c X DBA/2)F1 mice inoculated with 1 X 10(5) L1210/GZL cells were treated with IP injections of 27 micrograms anti-L1210 conjugate 1 h and 5 days after tumor cell inoculation, a life-prolonging effect was observed. [Lifespan in treated animals as percentage of that in controls (T/C) = 146%]. However, when the dose per injection was increased to 50 micrograms per mouse, survival was the same as in the control group. Postmortem examination of mice that had been treated with 50 micrograms anti-L1210 conjugate revealed lesions with necrosis and hemorrhage in the liver parenchyma and the intestinal epithelium, respectively. A similar toxic effect on the host mice was also observed with nonimmune conjugate.
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PMID:Ricin A-chain conjugated with monoclonal anti-L1210 antibody. In vitro and in vivo antitumor activity. 655 5

The monoclonal antibody W6/32.1 recognizes a public determinant on the HLA-A, B and C antigens of all tested human haplotypes. Though the antibody does not bind to normal mouse cells of any H-2 haplotype, it does show an unexpected specificity for the T cell leukemia line MBL-2 from a C57BL/6 mouse. It is shown that the murine antigen recognized by W6/32.1 is on an H-2-like molecule which also carries the determinant recognized by the monoclonal antibody B22-249 R1, specific for the H-2Db antigen. Unlike B22-249 R1, however, W6/32.1 does not bind to normal H-2b lymphocytes, nor to a variety of tumor cell lines of the H-2b haplotype. This cross-reaction is specific to W6/32.1, and is not shared by other monoclonal antibodies of similar anti-HLA specificities. Moreover, the affinity of W6/32.1 for its human antigen is substantially higher than for its mouse antigen. We conclude that W6/32.1 fortuitously recognizes a novel determinant on the H-2Db antigen of MBL-2, rather than an extensive region of structural homology shared between HLA and H-2. Thus for cells of the H-2b allotype this determinant is detected only on MBL-2, and by definition is thus an example of a tumor-associated antigen.
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PMID:A monoclonal anti-HLA antibody recognizes a mouse tumor-associated antigen. 660 Oct 10


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