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Biomedical subjects

J Ritz

Publications and source records attributed to J Ritz.

At least 217 records · Page 12Linked to original sources
PubMed1983

Establishment of a Ph1-positive human cell line (BV173).

A new cell line (BV173) derived from a patient with Philadelphia chromosome (Ph1)-positive acute leukemia was compared with the Ph1-positive K562 and NALM-1 lines, which display the phenotypic characteristics of erythroid and pre-B cells, respectively. BV173 cells retained the Ph1 chromosome and had the morphologic and cytochemical features of undifferentiated blast cells. They lacked the membrane characteristics of mature B- or T-lymphocytes and did not react with monoclonal antibodies to the myelomonocytic cell lineage. Although they reacted with anti-glycophorin A antiserum, they failed to produce hemoglobin after butyric acid treatment. This line was similar to NALM-1 in that it bore common acute lymphoblastic leukemia antigen and la-like antigen, reacted with monoclonal antibodies directed against early stages of hematopoietic cell differentiation, and presented the nuclear enzyme terminal deoxynucleotidyl transferase. However, it differed from NALM-1 because it did not express cytoplasmic IgM, a marker of pre-B-cells. The new line can be considered a clonal expansion of leukemia cells blocked at an earlier differentiation stage than that for the other Ph1-positive cell lines.

Antibodies, Monoclonal↗
PubMed1982

Autologous bone-marrow transplantation in CALLA-positive acute lymphoblastic leukemia after in-vitro treatment with J5 monoclonal antibody and complement.

A monoclonal antibody (J5) specific for the common acute-lymphoblastic-leukaemia antigen (CALLA) was used for in-vitro pre-treatment of bone-marrow before autologous transplantation in four patients with CALLA-positive acute lymphoblastic leukaemia (ALL) in relapse, who did not have HLA-compatible donors. After remission induction and intensification, bone-marrow cells were harvested, treated with J5 antibody and rabbit complement, and cryopreserved in liquid nitrogen. Patients received ablative chemotherapy and total-body irradiation before reinfusion of autologous J5-treated bone marrow. The transplantation protocol was well tolerated, and engraftment of normal myeloid cells occurred in all for patients. Two patients have continued in unmaintained remission with complete haematopoietic reconstitution for more than 1 year after autologous transplantation.

Antibodies, Monoclonal↗
PubMed1982

Induction of human B cell antigens in non-T cell acute lymphoblastic leukemia.

Leukemic cells from 70% of patients with Ia+CALLA+ non-T cell acute lymphoblastic leukemia (ALL) express an antigen (B1) found on all normal B lymphocytes. In this study, ALL cells that do not express the B1 antigen were studied in an attempt to further elucidate the cellular lineage of these tumors. Non-T cell ALL lines and tumor cells isolated from patients with non-T cell ALL that are Ia + CALLA + B1- were studied in vitro with a variety of agents known to promote cellular differentiation. Phorbol diester (TPA) or phytohemagglutinin conditioned leukocyte culture media were capable of inducing the expression of B1 on all four non-T cell ALL lines tested. In contrast, B1 could not be induced under the identical conditions on a promyelocytic leukemia line or a T cell lymphoblastic leukemia line. With the induction of B1 on non-T cell ALL lines, cytoplasmic mu-heavy chain (c mu) became undetectable, whereas the expression of CALLA and Ia were unchanged. The expression of B1 was accompanied by a decrease of cellular proliferation and DNA synthesis, but not significant morphologic changes were noted. In addition, no other B or T cell antigens were detected. The cellular origin of non-T cell ALL was further investigated using tumor cells isolated from leukemic patients. Tumor cells from eight patients with Ia + CALLA + B1-c mu- ALL could be induced in vitro with TPA to express both B1 and c mu. In contrast, cells from five patients with Ia + CALLA-B1-c mu- non-T cell ALL could not be induced with TPA to express CALLA, B1 or c mu. These studies suggest that the non-T cell ALL are heterogeneous and represent a spectrum of early B cell differentiation including the pre- pre-B cell (Ia + CALLA + B1-c mu-), the intermediate pre-B cell (Ia + CALLA +B1 + c mu-), and finally the "true" pre-B cell (Ia + CALLA + B1 + c mu+). The cellular origin of the remaining Ia + CALLA-B1-c mu- form of non-T cell ALL (20%) is still unknown.

Antigens↗
PubMed1982

Monoclonal antibody-ricin A chain conjugate selectively cytotoxic for cells bearing the common acute lymphoblastic leukemia antigen.

The toxic subunit of ricin has been conjugated by a disulfide bound to a monoclonal murine antibody (J-5) specific for the common acute lymphoblastic leukemia antigen (CALLA) expressed on human lymphoblastic cells. Both the monoclonal antibody and ricin A chain retained their original biological activity after conjugation. The ricin A chain portion of this conjugate effectively inhibited protein synthesis in a cell-free rabbit reticulocyte lysate system. Its antibody-combining site attached to the membrane of CALLA-bearing cells, whereupon both components of the molecule, antibody and A chain, could be detected using fluorescein-labeled antibody probes directed against either mouse F(ab')2 or ricin A chain. This conjugate proved to be a potent cytotoxin for CALLA-positive Nalm-1 cells growing in vitro and produced 50% inhibition of proliferation at levels of 2 x 10(-10) M. In contrast, CALLA-negative cell lines were unaffected until levels of conjugate approached 10(-6) M. When tested for cytotoxic action on Nalm-1 cells, the composite conjugate molecule was at least 2000 times more effective than J-5 antibody alone, ricin A chain alone, or a noncovalent mixture of these components. Cytotoxicity of the conjugate could be blocked completely by addition of antibodies specific for either mouse immunoglobulin or ricin A chain. Direct comparison of the in vitro cytotoxicity of CALLA-directed univalent Fab versus bivalent F(ab')2 carriers of ricin A chain revealed 70-fold greater efficacy for the latter conjugate. This differential could not be accounted for by differences in A chain activity or binding affinity for the cell membrane but appeared related to the ability of the multivalent agent to induce modulation and internalization of CALLA determinants. No overt toxic effects were noted when the F(ab')2-A chain conjugate was administered i.v. to rabbits at levels as high as 20 mg/kg single injection or 5 mg/kg for 5 days. The unique specificity characteristics and high potency of this cytotoxic conjugate indicate that it has significant therapeutic potential for the treatment of CALLA-bearing human leukemias and lymphomas.

Animals↗
PubMed1982

Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma.

The generation of murine monoclonal antibodies reactive with human leukemia and lymphoma cells has recently led to clinical trials that have begun to evaluate the use of these reagents in the treatment of various leukemias and lymphomas. Several of these studies have demonstrated that infusion of monoclonal antibody can cause the rapid and specific clearance of leukemic cells from the peripheral blood. Intravenously administered antibody also rapidly binds to bone marrow lymphoblasts, and in one instance, has resulted in the partial regression of tumor cell infiltrates in lymph nodes and skin. Unfortunately, clinically significant responses have not in general been achieved, but these clinical studies have identified specific factors that result in the development of resistance to antibody-mediated lysis in vivo. These factors include the presence of circulating antigen, antigenic modulation, reactivity of monoclonal antibody with normal cells, immune response to murine antibody, and the inefficiency of natural immune effector mechanisms. Current research is now being directed towards developing methods to circumvent each of these obstacles. Future clinical studies utilizing antibodies in vitro or with different specificity may demonstrate greater therapeutic efficacy. In addition, monoclonal antibodies can be used as carriers of other cytotoxic agents and in conjunction with other agents that will reduce the total load. Monoclonal antibodies represent new and powerful reagents that may in the near future become an additional therapeutic modality for patients with malignant disease.

Animals↗
PubMed1982

Generation of a cloned NK cell line derived from the "null cell" fraction of human peripheral blood.

The present studies were designed to determine the conditions for generation of human NK clones. First the "null cell" (NC) fraction of human peripheral blood mononuclear cells, which contains the NK effectors, was purified using negative selection with anti-T3, anti-T8, anti-B1, and anti-Mo2 monoclonal antibodies. Subsequently, NC were cloned by limiting dilution using a combination of phytohemagglutinin (PHA) and lymphocyte-conditioned medium (LCM) as an initial stimulus. Colonies could be easily obtained with this procedure, but the maintenance of long-term growth of the cultures represented a major problem. A cloned cell line termed JT1 was generated and has been proliferating continuously in culture for more than 6 mo. The phenotype of JT1 cells was analyzed several times with a series of monoclonal antibodies. These cells did not express surface markers related to thymic (T3-, T4-, T8-, T11-), B cells (B1-, J5-), or myelomonocytic (Mo1-, Mo2-, MY7-) differentiation. In contrast, 95% of JT1 cells reacted with the anti-T10 monoclonal antibody. T9, Ia, and J2 antigens were also present on JT1 cells, but their expression appeared variable from one determination to another. This cloned cell line maintains a strong cytotoxicity against common NK targets, such as K562 and Molt 4 cell lines, and a moderate ADCC activity. In addition, after several months in culture, JT1 cells are still capable of being regulated by interferon, because this lymphokine rapidly enhances cytotoxicity against K562 cells.

Antibodies, Monoclonal↗
PubMed1981

Comparative expression of T9, T10, and Ia antigens on activated human T cell subsets.

In the present study, the expression of three surface molecules T9, T10, and Ia, which are found on activated T lymphocytes, was examined utilizing monoclonal antibodies and indirect immunofluorescence. These antigens were shown to appear on T lymphocytes in a defined temporal sequence which was dependent on the specific triggering stimulus. Moreover, when T cells were fractionated into individual subsets of T4+ inducer and T8+ cytotoxic/suppressor lymphocytes, the expression of all three molecules was restricted to the T4+ subset following soluble antigen stimulation. By contrast, both subsets expressed these surface determinants following mitogen or alloantigen stimulation. The above results suggest that there may be successive stages in the T cell activation process associated with the appearance of unique cell surface antigens and further support the view that various triggering stimuli activate T cell populations differently.

Antibodies, Monoclonal↗
PubMed1981

Human cell lines express multiple populations of Ia-like molecules.

Three monoclonal antibodies have been used to isolate Ia-like antigens from three human cell lines; two of which are thought to be homozygous at the HLA-D/DR locus. Complete extraction of the Ia antigens identified by one antibody leaves those recognized by the two remaining antibodies in three parallel sets of experiments, indicating that the antigenic determinants recognized by these antibodies are present on three different populations of Ia molecules from cells of single individuals. These three populations of Ia-like molecules may reflect serologic variants of the product of a single genetic locus or may represent the products of as many as three nonallelic genetic regions. Demonstration of the existence of these multiple populations of Ia-like molecules on presumed homozygous typing cells indicates that this antigenic system is much more complex than has been generally realized. Further study may clarify the relationship between HLA-D/DR type and susceptibility to a variety of diseases and ultimately lead to better matches and improved survival for allogenic transplants. Since the HLA-D region is intimately involved in regulation of the immune response and susceptibility to a variety of diseases, use of monoclonal antibodies specific for discrete Ia antigens, the only identified products of the HLA-D region, may facilitate dissection of its many biological functions.

Antibodies, Monoclonal↗
PubMed1981

A unique cell surface antigen identifying lymphoid malignancies of B cell origin.

A monoclonal antibody (anti-B1) specific for a unique B cell surface differentiation antigen was used to characterize the malignant cells from patients with leukemias or lymphomas. All tumor cells from patients with lymphomas or chronic lymphocytic leukemias, bearing either monoclonal kappa lambda light chain, expressed the B1 antigen. In contrast, tumor cells from T cell leukemias and lymphomas or acute myeloblastic leukemia were unreactive. Approximately 50% of acute lymphoblastic leukemias (ALL) of non-T origin and 50% of chronic myelocytic leukemia in blast crisis were also anti-B1 reactive. moreover, 21 of 28 patients with the common ALL antigen (CALLA) positive form of ALL were anti-B1 positive, whereas 0 of 13 patients with CALLA negative ALL were reactive. These observations demonstrate that an antigen present on normal B cells is expressed on the vast majority of B cell lymphomas and on approximately 75% of CALLA positive ALL, suggesting that these tumors may share a common B cell lineage.

Antibodies↗
PubMed1981

Expression of myeloid differentiation antigens on normal and malignant myeloid cells.

A series of monoclonal antibodies have been characterized that define four surface antigens (MY3, MY4, MY7, and MY8) of human myeloid cells. They were derived from a fusion of the NS-1 plasmacytoma cell line with splenocytes from a mouse immunized with human acute myelomonocytic leukemia cells. MY3 and MY4 are expressed by normal monocytes and by greater than 90% of patients with acute monocytic leukemia or acute myelomonocytic leukemia, but are detected much less often on other types of myeloid leukemia. MY7 is expressed by granulocytes, monocytes, and 5% of normal bone marrow cells. 79% of all acute myeloblastic leukemia (AML) patients tested (72 patients) express MY7 without preferential expression by any AML subtype. MY8 is expressed by normal monocytes, granulocytes, all peroxidase-positive bone marrow cells, and 50% of AML patients. MY3, MY4, and MY8 define myeloid differentiation antigens in that they are not detected on myeloid precursor cells and appear at discrete stages of differentiation. These antigens are not expressed by lymphocytes, erythrocytes, platelets, or lymphoid malignancies. The monoclonal antisera defining these antigens have been used to study differentiation of normal myeloid cells and malignant cell lines.

Animals↗
PubMed1981

Cell surface characterization of malignant T cells from lymphoblastic lymphoma using monoclonal antibodies: evidence for phenotypic differences between malignant T cells from patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.

A series of monoclonal antibodies was used for the characterization of malignant T cells from 21 patients with lymphoblastic lymphoma (LL). The tumor population from these patients showed a marked degree of phenotypic heterogeneity and a proportion (one-third) of patients had tumor cells that did not conform exactly with the cells normally detected in the thymus. However, these cell populations could be related to the early or common or late thymocyte population (about one-third of the patients in each category). This contrast, with the characterization of malignant T cells from 43 patients with acute lymphoblastic leukemia (ALL) that could be related to either early or common thymocytes, with an exception of two patients categorized as having a tumor population related to late thymocytes. Further phenotypic differences between cells from ALL and LL could be demonstrated by investigation with two additional monoclonal antibodies, A50 and U4. Among patients with malignant T cells related to common thymocyte, 0/12 patients with ALL had cells recognized by A50, where 5/8 patients with LL had A50+ cells. Among patients with early thymocytes, only patients with ALL had cells recognized by U4. In addition, 5 LL patients had cells reactive with J5, a monoclonal antibody recognizing the common ALL antigen (CALLA). Since CALLA was found on cells related to common and late thymocytes, CALLA is neither lineage specific, nor can it be viewed as being peculiar to malignant lymphoid cells arrested at very immature stages of differentiation.

Adolescent↗
PubMed1981

Serotherapy of acute lymphoblastic leukemia with monoclonal antibody.

We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

Adolescent↗
PubMed1981

Fate of a common acute lymphoblastic leukemia antigen during modulation by monoclonal antibody.

Modulation of a human common acute lymphoblastic leukemia antigen (CALLA) by specific monoclonal antibody (J5) has been studied with the immune precipitation method to identify radiolabeled antigen. Surfaces of leukemic cells have been labeled using 125I both before and after modulation by J5 antibody for different time intervals. Leukemic cells have also been metabolically labeled with 35S-methionine before modulation. These studies indicate that the 100,000-dalton glycoprotein expressing CALLA (gp 100-CALLA) cannot be detected in cells that were modulated with J5 antibody before surface labeling but that it is easily detectable in cells that were surface labeled before modulation for 10 hr. At later time points, gp 100-CALLA is selectively lost from cells that were surface labeled before modulation. Gp 100-CALLA is not detected in the supernatants from cultures of these modulated cells. We conclude that gp 100-CALLA is rapidly internalized during modulation and that CALLA is degraded. Gp 100-CALLA is not shed into the culture media, nor does it remain on the cell surface in an altered form. Incubation of leukemic cells with antisera to beta2-microglobulin or IgM does not affect the expression of gp 100-CALLA.

Antibodies, Neoplasm↗
PubMed1981

Absence of common ALL antigen on normal bipotent myeloid, erythroid, and granulocyte progenitors.

The presence of the common acute lymphoblastic leukemia antigen (CALLA) on leukemic cells from the great majority of patients with non-T cell acute lymphoblastic leukemia and chronic myelogenous leukemia in blast crisis suggests that CALLA could be differentiation antigen expressed by normal lymphoid and myeloid stem cells. Treatment with a murine monoclonal anti-CALLA antibody and complement lysed CALLA-positive leukemic cells quantitatively, whereas similar treatment of nucleated cells from peripheral blood and bone marrow failed to affect the expression, in semisolid culture, of CFU-G/E, BFU-E, CFU-E, or CFU-C. These data suggest that CALLA is not a normal differentiation antigen of the myeloid bipotent cell or its committed progenitors.

Acute Disease↗