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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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).

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.

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.

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.

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.