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J Ritz

Publications and source records attributed to J Ritz.

232 records · Page 13Linked to original sources
PubMed1981

Use of monoclonal antibodies as diagnostic and therapeutic reagents in acute lymphoblastic leukemia.

A monoclonal antibody specific for a common acute lymphoblastic leukemia (ALL) antigen has been generated and characterized. This antibody (J-5) is reactive with leukemic cells from most patients with non-T-cell ALL and some patients with chronic myelocytic leukemia in blast crisis. J-5 antibody is not reactive with leukemic cells from patients with either T-cell ALL, chronic lymphocytic leukemia, acute myeloblastic leukemia, or stable-phase chronic myelocytic leukemia. In addition to diagnostic applications, anti-common ALL antigen monoclonal antibody has been used to study the effect of specific serotherapy in the treatment of ALL. In the first patient with ALL treated with J-5 antibody, a 90% reduction in circulating lymphoblasts occurred within 1 hr of starting antibody infusion. Despite continued serotherapy, however, lymphoblasts persisted in peripheral blood and bone marrow. Analysis of cell surface markers during serotherapy suggested that resistance to antibody-mediated lysis in vivo may have been due to antigenic modulation of leukemic cells in response to J-5 monoclonal antibody.

Acute Disease↗
PubMed1981

Surface antigens on malignant Sézary and T-CLL cells correspond to those of mature T cells.

Tumor cells from eight adult patients with T-cell chronic malignancies were investigated with a series of monoclonal antibodies recognizing T-cell differentiation antigens. This series allowed definition of discrete subpopulations of mature T cells with functional specialization. All six patients with Sézary syndrome and one patient with T-chronic lymphocytic leukemia had cells with the same phenotype as normal helper/inducer T cells, whereas the other patient with T-chronic lymphocytic leukemia had cell with the same phenotype as normal cytotoxic/suppressor T cells. Some clinical manifestations observed in these patients may reflect retention of functional activities by their malignant cells.

Antibody Specificity↗
PubMed1981

Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage.

Previous studies have demonstrated that the common acute lymphoblastic leukemia antigen (CALLA) is expressed by leukemic cells from approximately 80% of patients with non-T-cell ALL and 30%-50% of patients with chronic myelocytic leukemia in blast crisis. A small number of normal bone marrow and fetal liver cells also express CALLA, but the functional role of this molecule is unknown. In the present study, we have used a monoclonal antibody (J5) specific for CALLA to study the expression of this antigen in non-Hodgkin's lymphomas. Within the B-cell lymphomas, it was found the CALLA was expressed by almost all Burkitt's and nodular poorly differentiated lymphocytic lymphomas. Within the T-cell lymphomas, CALLA was expressed in 40% of patients with lymphoblastic lymphoma. Three of 3 Burkitt's lymphoma cell lines and three of eight T-lymphoblast cell lines were also found to express CALLA. Normal spleen, lymph node, and thymus cells were not reactive with J5 antibody. These findings indicate that expression of CALLA is not limited to relatively undifferentiated leukemic lymphoblasts but also occurs in more differentiated lymphoid malignancies. However, normal differentiated lymphoid cells in lymph node, spleen, and thymus, which have a phenotype similar to that of lymphoma cells, do not appear to express CALLA.

Antigens, Neoplasm↗
PubMed1980

A monoclonal antibody to human acute lymphoblastic leukaemia antigen.

Previous studies by Greaves and others have demonstrated the existence of an antigen associated with cells from many patients with acute lymphoblastic leukaemia (ALL) and some patients with chronic myelocytic leukamemia (CML) in blast crisis. Antisera to this common ALL antigen (CALLA) have been produced in rabbits and require extensive absorption which limits both the titre and quantity of antisera that can be generated and may result in variable specificity in different laboratories. The method for generation of specific antibody by somatic cell hybridisation introduced by kohler and Milstein has been successfully used to produce monoclonal antibodies against various normal human cell-surface proteins, including beta 2 microglobulin, histocompatibility antigens, thymocyte and peripheral T-cell antigens and Ia-like antigens. The present report describes the generation and characterisation of a monoclonal antibody specific for a common ALL antigen (CALLA) previously identified by conventional heteroantisera.

Animals↗
PubMed1980

Cell surface antigens: prognostic implications in childhood acute lymphoblastic leukemia.

Lymphoblasts from 93 children with acute lymphoblastic leukemia (ALL) were characterized by immunologic cell surface markers. These patients were treated on a single protocol, featuring adriamycin therapy during remission, and have been followed from 2 to 6.5 yr (median 4 yr). Three classes of patients were defined serologically: HTA+ Ia- CALLA-, Ia+ CALLA+ HTA-, and Ia+ CALLA- HTA-. Disease-free survival and sites of relapse were assessed within immunologic subsets. Similar to the findings of others, T-cell (HTA+ Ia-) patients fared poorly as compared to non-T-cell (Ia+ HTA-) patients (median disease-free survival was 12 and 47 mo. respectively; p = 0.0004). The majority of relapses in the HTA+ patients occurred at extramedullary sites. Late testicular relapse was rare among Ia+ patients. In addition, the "common ALL antigen" (CALLA) may identify a relatively favorable subset within the Ia+ population. The prognostic value of the immunologic markers was compared with traditional clinical factors. There was much overlap between HTA+, older age, and elevated WBC. However, neither age nor WBC alone were of prognostic significance among the Ia+ patients. We conclude that surface markers define both biologic and prognostic characteristics. The course of childhood ALL must be viewed in the context of homogeneous subsets and within particular therapeutic programs.

Antigens, Neoplasm↗
PubMed1980

Human leukemia-associated antigen: relation to a family of surface glycoproteins.

A heteroantiserum raised to leukemic cells of a patient with non-T cell acute lymphoblastic leukemia (ALL) has been extensively absorbed with cells from a leukemic T cell line and an autologous B lymphoblastoid cell line to produce a common ALL antiserum (CALLA). CALLA is specific for leukemic cells of most patients with non-T cell ALL and chronic myelogenous leukemia (CML) in lymphoid blast crisis. It has been extensively tested on a wide variety of normal cells and is unreactive with them. CALLA identifies a surface glycoprotein having a m.w. of approximately 100,000 on reactive cell populations. In contrast, partially absorbed anti-ALL sera detect a similar glycoprotein band on CALLA-negative B and T cell lines. The glycoprotein identified by CALLA has been isolated and used as an immunogen. This new antiserum (C129) detects a 100,000-dalton glycoprotein not only on CALLA-positive cell populations but also on most CALLA-negative normal and malignant hematopoietic cells and on B and T cell lines. We conclude that there exists a family of 100,000-dalton glycoproteins that are present on a variety of normal, transformed, and malignant cells and that possess shared as well as unique antigenic regions. The expression of at least one of these antigens, detected by CALLA, may be tumor specific.

Animals↗
PubMed1979

Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression.

The nature of Ia antigens which appear on human T cells after activation and the stimuli required for their expression was examined utilizing a monoclonal antibody reactive with the Ia antigen framework. T cells were purified using monoclonal antibodies directed either at the entire T-cell population (OKT3) or the T-cell inducer subset (OKT4). By indirect immunofluorescence, it was shown that the human T-cell population contains no detectable Ia+ cells in the resting state. In contrast, in excess of 60% of the T-cell population expresses Ia antigen after alloactivation in the mixed lymphocyte culture. Moreover, these Ia antigens are expressed within both the OKT4+ and OKT4- subsets. Similarly, phytohemagglutinin and concanavalin A induced approximately 20% of peripheral T cells to express Ia antigen and the expression of these antigens is not restricted to either OKT4 subset. In contrast, only the inducer T-cell population which proliferates maximally to soluble antigen expresses Ia antigens after activation by tetanus toxoid. Thus, the expression of human Ia antigens on unique T-cell subsets depends upon the activation stimuli utilized and ability of the individual subset to respond to a given stimulus. Additional studies indicated that Ia antigens appear on previously Ia- T cells after activation and do not result from clonal expansion of a small subset of Ia+ T cells.

Antigen-Antibody Reactions↗
PubMed1979

Leukemia-associated antigens in ALL.

A cytotoxic common ALL antiserum (CALLA) specific for leukemic cells of most patients with non-T-cel- acute lymphoblastic leukemia (ALL) and of some patients with chronic myelogenous leukemia (CML) in blast crisis has been reproducibly prepared using cell lines for absorption. CALLA reacts with leukemic cells of 110 of 134 patients (82%) with non-T-cell ALL; 1 of 71 (1%) patients with acute myelogenous leukemia (AML); 2 of 7 patients (29%) with chronic myelogenous leukemia in blast crisis; 7 of 92 patients (8%) with other hematologic malignancies; and with the leukemic cell lines Laz 221 and NALM-1. It does not react with the normal hematopoietic cells, B- or T-cell lines, or cells from 26 patients with T-cell ALL that were tested. CALLA reactivity and periodic acid Schiff (PAS) staining correlate poorly, with CALLA reacting with cells from 86% (64 of 74) of patients with PAS-positive and 76% (29 of 38) of those with PAS-negative non-T-cell ALL. In these patients, CALLA reacts with cells from 89% of those under age 12 (78 of 88); 74% of those aged 12--20 (20 of 27); and 58% of those over 20 (11 of 19). Using only CALLA and antisera specific for Ia-like and T-cell antigens, we can now distinguish most cases of ALL from AML and other hematologic malignancies.

Absorption↗
PubMed1976

Systemic mastocytosis associated with presence of rheumatoid factor.

We encountered a case of systemic mast cell disease associated with rheumatoid factor; to our knowledge, this has not been reported in the literature. Rheumatoid arthritis as an unrelated second disease cannot be excluded, but there is support for a relation between joint symptoms, rheumatoid factor, and the mast cell disease.

Female↗
PubMedDate not supplied

Preparation and characterization of interleukin-2-gelonin conjugates made using different cross-linking reagents.

Conjugates of IL-2 with the ribosome-inactivating protein gelonin were prepared using heterobifunctional reagents to link the proteins via disulfide, acid-labile, and noncleavable linkers. In each case, one protein was modified using 2-iminothiolane. The sulfhydryl groups so introduced were then reacted either with 2-nitro-5-dithiobenzoate groups or with iodoacetamido groups which had been introduced into the second protein. In the case of the acid-labile linkage, a reagent which forms a labile bond upon reaction with amino groups, 4-(iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride (its synthesis is described in this paper) was used to modify the toxin. The conjugates were separated from nonconjugated proteins by gel filtration on Sephadex G100 (SF). Each was analyzed with respect to its ribosome-inactivating activity, its ability to bind to the IL-2 receptor, and its in vitro cytotoxicity. The ribosome-inactivating activity of gelonin was unaffected by modification with 2-iminothiolane and was retained in conjugates prepared using this reagent. Modification of the toxin with 4-(iodoacetamido)-1-cyclohexene-1,2-dicarboxylic acid anhydride to form the acid-labile link drastically reduced the activity of the toxin. However, the activity of the toxin was recovered following acid treatment to release the native protein. Conjugates containing each type of linkage exhibited both specific binding and selective cytotoxicity toward cells expressing the IL-2 receptor. The most potent of these toxins, that containing the disulfide linkage, exhibited a cytotoxicity which was 2 orders of magnitude greater than that of unconjugated gelonin.

Animals↗
PubMedDate not supplied

Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein.

The T11 sheep erythrocyte binding glycoprotein [relative molecular mass (Mr)50,000(50K)] is expressed throughout human T-lymphocyte ontogeny and appears to play an important physiological role in T-cell activation. Thus, the treatment of T cells with certain monoclonal anti-T11 antibodies results in antigen-independent polyclonal T-cell activation as assessed by proliferation and lymphokine secretion. In addition, the majority of thymocytes that have not yet acquired the T3-Ti antigen/major histocompatibility complex (MHC) receptor can be activated to express interleukin-2 (IL-2) receptors through this T11 structure. We show here that the triggering of cytolytic T (Tc) cells via T11 causes an antigen-independent activation of the cytolytic mechanism as evidenced by the induction of nonspecific cytolytic activity. Furthermore, T11+T3-Ti- natural killer (NK) cell clones can also be induced to lyse NK-cell-resistant targets by treatment with anti-T11 monoclonal antibodies directed at defined T11 epitopes. These results indicate that T11 triggering can activate cytotoxic lymphocytes to express their functional programmes in the absence of specific antigen recognition via the T3-Ti complex and provide further evidence for the notion that certain NK cells and T lymphocytes are related.

Animals↗
PubMedDate not supplied

Specific release of proteoglycans from human natural killer cells during target lysis.

Natural killer (NK) activity is mediated by a small population of peripheral blood cells that exhibit the homogeneous morphology of large granular lymphocytes (LGL). In recent studies, human NK cell clones have been shown to contain a 200,000-Mr (relative molecular mass) protease-resistant chondroitin sulphate A proteoglycan, which has been localized to the secretory granule by X-ray dispersive analysis and by its resistance to cleavage by extracellular addition of chondroitinase AC or ABC (ref. 7). In the present study, we have used six different human NK cell clones to demonstrate that release of 35S-proteoglycan correlates closely with cytolytic activity against various NK cell targets. When NK activity is blocked by monoclonal antibodies at either the effector cell level (LFA-1) or at the target cell level (TNKTAR), there is a concomitant decrease in exocytosis of proteoglycan. Monoclonal antibodies directed against recognition structures, for example anti-NKTa and anti-T3 (ref. 10), function as soluble stimuli, capable of initiating the release of 35S-proteoglycan. Taken together, these results provide strong evidence for the stimulus-specific release of chondroitin sulphate A proteoglycans from NK cells when the cytolytic process is activated.

Antibodies, Monoclonal↗
PubMedDate not supplied

Costimulation of human natural killer cell proliferation: role of accessory cytokines and cell contact-dependent signals.

Despite the importance of natural killer (NK) cells in the immune response, the regulation of human NK cell growth has not been well characterized. We have hypothesized that, similar to the proliferation of T and B lymphocytes, optimal proliferation of NK cells requires costimulatory signals as well as a primary mitogenic stimulus. Evidence for costimulation by both soluble cytokines and cell contact-dependent factors is presented. Soluble IL-1 and TNF were found to augment NK cell proliferation in response to primary mitogenic cytokines, including IL-2, IL-4, IL-7, and IL-12. The costimulatory effect of IL-1 and TNF is strongly enhanced by the calcium ionophore ionomycin. Coculture of NK cells with irradiated K562 cells can largely substitute for the costimulatory signal provided by ionomycin. Costimulation by K562 requires intimate cell contact and is not reconstituted by cell-free supernatants. Activated T lymphocytes can also mediate contact-dependent costimulation of NK cells; resting PBMC, several NK-sensitive cell lines, and all NK-resistant cell lines tested were not found to be costimulatory. Engagement of CD16 did not augment NK cell proliferation. Thus, triggering of natural killing or antibody-dependent cell-mediated cytotoxicity (ADCC) does not consistently provide a costimulatory signal for NK cell proliferation. Cell contact-dependent costimulation of NK cells does not appear to involve known receptors that can costimulate T cells, including CD2, CD27, CD28, CD29, or LFA-1. The molecular nature of the putative NK cell costimulatory receptor remains to be elucidated. Nevertheless, human NK cells could be expanded in vitro using leukocyte-conditioned medium (LCM) as a source of IL-2 and accessory cytokines and ionomycin to bypass the putative receptor for cell contact-dependent costimulation. NK cells expanded in LCM and ionomycin express typical NK cell antigens and mediate natural killing and ADCC. Further characterization of the costimulatory signals for NK cell proliferation may elucidate the physiologic regulation of NK cell growth and may ultimately allow more effective manipulation of these lymphocytes in the immunotherapy of human diseases.

Antibody-Dependent Cell Cytotoxicity↗