Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.
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PMID:Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19). 128 Oct 55

The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (HIV-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta-chain [CT beta] rearrangement) and phenotypically (CD45RO+, CD4+, CD5+, CD25+, CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4+, CD25+ (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R RNA is analogous to human T-lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated HIV-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphoma in which HIV-1 infection may have played a central role in the lymphocyte transformation process.
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PMID:Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation. 137 87

In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.
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PMID:Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells. 140 55

The initial site of disease relapse was identified for 79 patients with metastatic renal cell cancer (RCC), melanoma, colon cancer, or non-Hodgkin's lymphoma (NHL), who had achieved partial or complete responses to one of five IL-2-based immunotherapy regimens. The initial site of relapse was evenly distributed between pre-existing sites of disease (33%), new sites of disease (38%), or both (29%). There was no difference in the distribution of recurrences between patients with partial or complete responses. Fifty-one patients with prior complete or partial responses were retreated with additional IL-2-based therapy following tumor progression. Five of 51 patients retreated following relapse developed new partial responses. There were no complete responses. Three patients with NHL were retreated with IL-2 and LAK cells and all achieved a second response, while only 2 of 48 patients with other histologic diagnoses reresponded. It is concluded that after a partial or complete response to IL-2-based immunotherapy, patients who relapse do so equally at new and pre-existing sites of disease. A response to retreatment following tumor progression may be attained in patients with NHL, while a new response is unlikely for patients with melanoma and RCC.
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PMID:Relapse after response to interleukin-2-based immunotherapy: patterns of progression and response to retreatment. 179 Jan 45

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.
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PMID:Immunologic markers in non-Hodgkin's lymphoma. 193 59

Using five different cell lines as reactive cells, the proliferative inhibitory effect of Con A induced suppressive cells (CISC) was observed. The percentage of inhibition of MLA144 was 93.1%, K562 77.5%, Raji 62.5%, Molt-4 46.4%, and P388 25.9%. It is possible that K562 and MLA144 can be used as reactive cells instead of the peripheral blood mononuclear cells. Supernatants of CISC were also shown to be inhibitory, although less so than CISC. The inhibitory activity of CISC did not seem to be related to prostaglandin. However, its activity could be diminished by anti-T11 monoclonal antibody and complement. These results indicate that CISC is a T11-positive lymphocyte population. The inhibitory activity of CISC from 48 normal donors was determined by this modified method and compared with that of 22 patients with non-Hodgkin's lymphoma. The CISC activity of the patients was significantly lower than that of the normal subjects. Addition of exogeneous IL-2 to the culture enhanced the inhibitory activity in both groups.
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PMID:[Characteristics of Con A induced cells and their inhibitory activities in patients with lymphoma]. 214 13

A 79-year-old female was admitted with dyspnea. Chest roentgenogram showed massive left-side pleural effusion. Chest CT scan and abdominal CT scan revealed marked swelling of mediastinal and para-aortic lymph nodes. Diagnosis of non-Hodgkin's lymphoma was made by pleural fluid cytology. Recombinant interleukin-2 (1000 units/day) was administered into the pleural cavity for 14 days continuously. Clinically, pleural effusions and malignant cells in the effusions disappeared. Immunologically, levels of IL-2 receptor positive cells, soluble IL-2 receptors and CD4 positive cells in the pleural effusion increased 7 days after recombinant IL-2 administration with subsequent decrease after completion of treatment. On the other hand, levels of IL-2 receptor positive cells, soluble IL-2 receptors and CD4 positive cells in the peripheral blood increased with no subsequent decrease after completion of treatment.
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PMID:[Intrapleural administration of recombinant interleukin-2 in a patient with pleural effusion due to non-Hodgkin's lymphoma]. 261 11

Malignant lymphoma is classified roughly into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) according to the biological characteristics. Malignant lymphoma in Japan has such characteristics as low incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma study, the introduction of molecular diagnosis by means of gene rearrangement analysis of immunoglobulin and T cell antigen receptor has contributed diagnostically to a definitive determination of T and B cell lineage and cellular monoclonality in malignant lymphoma. On the other hand, remarkable progress has been made in the treatment of malignant lymphoma in recent years. After all, in HD even far advanced cases have been expected to be curable by the combination chemotherapy, for example, MOPP regimen in USA at the present time. Furthermore, in NHL even advanced cases with such aggressive lymphoma as diffuse large cell lymphoma of B cell type have also been able to survive for more than 10 years and may be curable with the frequency of more than 30% in several institutions. Nowadays, the treatment for malignant lymphoma has focussed on multidisciplinary cure-oriented therapy including chemotherapy and radiotherapy in a collaboration of surgical procedure and immunotherapeutic maneuvers. The recent chemotherapy regimen has been called "third generation" ones characterized by alternating non-cross resistant combination and frequent administration of intense drug dose. Furthermore, various biologics such as monoclonal antibodies, several BRMs including IFNs, IL-2 and TNF, and recombinant G-CSF and GM-CSF have been applied in lymphoma treatment to improve the efficacy of combination chemotherapy in new designs of clinical trials.
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PMID:[Malignant lymphoma]. 273 35

Malignant B cells, derived from hairy cell leukemia (HCL), non-Hodgkin's lymphoma (NHL) or prolymphocytic leukemia were stimulated with mitogens and interleukin 2 after careful depletion of contaminating T cells resulting in final residual percentages of less than 0.1. No proliferation was found as measured by 3H-thymidine incorporation. Subsequently, to the non-T B cell cultures very small amounts of autologous or allogeneic T cells were added, ending up in final concentrations of 0.1, 0.5, 1, or 2% T cells. It appeared that a marked proliferation occurred which had in various coculture combinations to be ascribed to the T cells alone. Moreover, most HCL and other B cell NHL additionally stimulated the T cells, resulting in a further increase in proliferation. We conclude that 3H-thymidine incorporation by malignant B cells such as HCL and B-NHL stimulated with mitogens and IL-2 will in most cases wrongly be attributed to proliferation by the B cells themselves, and instead has to be ascribed to contaminating T cells.
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PMID:Residual T lymphocytes, and not malignant B cells, proliferate upon mitogenic stimulation. 278 26

The present study investigated the peripheral blood mononuclear cells (PBMC) blastic responses to PHA, PHA plus recombinant IL-2 (rIL-2) and rIL-2 alone; the expression of membrane-bound IL-2R on PHA-stimulated PBMC; and the levels of IL-1 alpha, IL-2, IL-6, and sIL-2R in serum and in culture supernatants from PHA-stimulated PBMC in 17 patients with with non-Hodgkin's lymphoma (NHL), 4 with Hodgkin's lymphoma (HL), 5 with Hairy cell leukemia, 1 with chronic myelogenous leukemia, and 1 with chronic lymphocytic leukemia. The patients with HL and NHL with active disease (AD) were separated from those in clinical remission. The patients with AD were studied at diagnosis (obviously before therapy) and the patients in clinical remission were out of therapy since at least 6 mo. The lymphocyte blastogenic response to PHA was significantly lower in patients with HL and NHL with AD than in the control group. The response to rIL-2 alone was in the same range in the control group and in HL and NHL AD patients. By adding rIL-2 to PHA there was an increase of the blastogenic response of the same patients. The percentage of CD25 expressed on PHA-stimulated lymphocytes from patients with HL and NHL AD and from normal subjects is in the same range. Serum levels of IL-2, IL-6, and sIL-2R were significantly higher in HL and NHL AD patients than in controls as well as in all other hematological malignancies. Supernatants derived from PHA-stimulated PBMC were assessed for the presence of cytokines and sIL-2R by ELISA. The levels of IL-2, IL-6, and sIL-2R were significantly lower in HL and NHL AD patients than in controls as well as in all other hematological malignancies.
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PMID:Membrane-bound/soluble IL-2 receptor (IL-2R) and levels of IL-1 alpha, IL-2, and IL-6 in the serum and in the PBMC culture supernatants from 17 patients with hematological malignancies. 749 95


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