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)

Five patients with non-Hodgkin's lymphoma (NHL) and 4 patients with chronic lymphocytic leukaemia (CLL) were treated with the CDR-grafted (rat x human) monoclonal antibody (mAb) Campath-1H (anti-CD52). Tumour regression was noted preferentially in peripheral blood and in the bone marrow but lymph nodes were less affected. Normal blood B and T cells were profoundly reduced in all patients whereas CD16+ NK cells and CD14+ monocytes decreased marginally. In all responding CLL patients CD52-negative T but not B cells appeared during treatment and persisted for several months (4-19+) during unmaintained follow-up. Clonal T cells defined as a predominance of a single T cell receptor (TCR) V gene usage, in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing, emerged within the CD52-/CD8+ cell population during Campath-1H therapy in 2 CLL patients, both achieving a long-lasting remission. The increase in CD8+ T cell expansions (up to 23-fold) during unmaintained remission and follow-up suggest that the clonal CD8+ cells may represent regulatory T cells controlling the growth of the tumour B cell clone. Clonal T cells might thus be a target for an immune therapeutic intervention in B cell tumours.
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PMID:Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients treated with Campath-1H (anti-CD52). 902 Mar 67

CAMPATH-1H is a humanized antilymphocyte monoclonal antibody (mAb) directed against the CD52 antigen expressed on normal and malignant lymphocytes. We report the results of a multicenter phase II trial using intravenous CAMPATH-1H in previously treated patients with nonbulky non-Hodgkin's lymphoma (NHL) or minimal residual NHL. Sixteen previously treated patients with nonbulky NHL and two patients with minimal residual NHL, were treated with CAMPATH-1H. Changes in peripheral blood lymphocyte subsets were analyzed by multiparameter flow cytometric techniques in eleven patients. The 18 patients enrolled in the studies received CAMPATH-1H for a median duration of 6 weeks (range, 3 to 14 weeks), and a median cumulative dose of 470 mg (range, 180 to 1185 mg). Two of the sixteen patients with nonbulky NHL achieved a complete response (CR) and one patient achieved a partial response (PR). One of the two patients with minimal residual NHL achieved a molecular CR. Infusional complications were seen with the majority of patients but were more common with initial infusions. Significant hematologic toxicity was also observed with grade (3/4) thrombocytopenia (n=10), grade (3/4) neutropenia (n=4) and grade 3 anemia (n=3). Due to excessive infectious complications observed with the patients enrolled, the trials were terminated early. Anti-tumor activity was demonstrated in a small subset of previously treated low-grade lymphoma patients with nonbulky or minimal residual disease. Future studies evaluating the effect of different drug schedules, modes of mAb administration, and concurrent use of prophylactic antibiotics/antiviral/antifungal agents to optimize anti-tumor activity and limit infectious toxicities are planned.
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PMID:A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin's lymphoma. 1134 59

The treatment options for chronic lymphocytic leukemia (CLL) beside standard therapy with chlorambucil or other alkylating agents have dramatically increased in the last few years. Promising results have been reported with new cytotoxic agents such as the purine analogues fludarabine and 2-chlordeoxyadenosine, either at first diagnosis or at relapse. Nevertheless, all patients with CLL relapse after initial response. Since residual lymphoma cells are very likely to be the origin of the clinical relapse, there is a need for new therapeutic approaches with different mechanism of action to eliminate these residual cells. These approaches include allogeneic or autologous stem cell transplantation as well as immunotherapeutic strategies. Monoclonal antibodies, either alone or conjugated to toxins or radioisotopes, are thus being actively investigated. In clinical trials the genetically engineered chimeric unconjugated anti-CD20 antibody Rituximab and the humanized unconjugated anti-CD52 antibody Campath-1H achieved the most promising results in the treatment of patients with relapsed or refractory low-grade non-Hodgkin's lymphoma. Thus far there is only little clinical experience with Rituximab in patients with CLL, and the exact role of these agent in the treatment of CLL has still to be determined in ongoing and future trials. As a single agent Campath-1H showed more clinical activity in previously treated CLL patients than Rituximab, with response rates of up to 33% in a multicenter pivotal study. Furthermore, the potential risks of tumor lysis and anaphylaxia for both antibodies and immunosuppression particularly for Campath-1H must be taken into account. The present review will compare the development and the basic principles of these unconjugated monoclonal antibodies and consider their present and potential role in the treatment of patients with CLL. Copyright 2000 S. Karger GmbH, Freiburg
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PMID:The Monoclonal Antibodies Campath-1H and Rituximab in theTherapy of Chronic Lymphocytic Leukemia. 1144 Dec 56

Monoclonal antibodies (mAb) have dramatically advanced our ability to treat non-Hodgkin's lymphoma (NHL), and there has been a virtual explosion of clinical data regarding their use. Rituximab is a humanized anti-CD20 mAb and has significant single agent activity in follicular lymphoma, and to a lesser extent in mantle-cell and diffuse large B-cell lymphoma (DLCL). Rituximab appears to have synergistic activity with cytotoxic chemotherapy and the combination has recently demonstrated improved rates of complete remission (CR) and overall survival in older patients with DLCL. Alemtuzumab (Campath-1H) is a humanized mAb targeting CD52 and has recently been approved in the USA for the treatment of fludarabine-refractory B-cell chronic lymphocytic leukaemia. Impressive activity has also been demonstrated in T-cell prolymphocytic leukaemia and mycosis fungoides. The radioconjugated anti-CD20 mAbs ibritumomab tiuxetan and I131-tositumomab also have impressive clinical activity in low-grade B-cell NHL, and the former has demonstrated superior CR rates to rituximab. Myelosuppression is more significant however, and their place in the treatment algorithm remains to be clearly defined. Other immunotoxins (e.g. BL22) and mAb against alternate targets (e.g. epratuzumab, humanized anti-CD22) are in development.
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PMID:Antibody-based therapy of non-Hodgkin's lymphoma. 1246 99

Rituximab (Mabthera) and alemtuzumab (Campath(R), Mabcampath(R)) are non-conjugated IgG1 therapeutic monoclonal antibodies directed against the CD20 and CD52 surface antigens respectively. They are presently used in the therapy of indolent B-cell non-Hodgkin's lymphoma (B-NHL) and of B-cell chronic lymphocytic leukaemia, and are thought to act mainly through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Here we have analysed the capacity of these two monoclonal antibodies to lyse cell lines of acquired immunodeficiency syndrome (AIDS)-related B-NHL through either complement activation or antibody-dependent cytotoxicity. Rituximab strongly activated both CDC and ADCC against CD20-positive AIDS-NHL cells lines, inducing up to 60-98% and 20% specific lysis respectively. In contrast, alemtuzumab was a poor activator of CDC, even in the AIDS-NHL cell lines expressing high amounts of CD52, leading to a lysis of only 1-30%, whereas it was at least as strong as rituximab in inducing ADCC of the same lines (up to 30% specific lysis). Altogether, these data offer a first in vitro rationale supporting the therapeutic use of rituximab for CD20-positive AIDS-NHL.
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PMID:Acquired immunodeficiency syndrome-associated lymphomas are efficiently lysed through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by rituximab. 1247 69

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia of adults in Western countries. It is a systemic haematological malignancy that originates from B cells (B-CLL) in 95% of patients, while only a minority are derived through malignant transformation of T cells (T-CLL). Although B-CLL is classified as a non-Hodgkin's lymphoma, several issues make this leukaemia a unique entity among malignant lymphoma. Inhibition of the programmed cell death (apoptosis) and upregulation of the anti-apoptotic protein Bcl-2 are key elements of the pathophysiology of B-CLL cells and define clinical prognosis. Furthermore, B-CLL cells are arrested in G0/G1 phase of the cell cycle. Dysfunctional apoptosis and cell cycle are the main reasons for the clinical enigma, that CLL can not yet be cured with conventional chemotherapy. However, the molecular pathways that are responsible for this characteristic feature of the B-CLL cells still need further definition.Recently, considerable progress has been made in defining the molecular basis for the pathogenesis of CLL and in finding new therapeutic options. Recent studies indicate that B-CLL cells may be delineated from two main groups of normal B cells, i.e. pre- and postgerminal B cells, and can be distinguished through lack of or existence of mutations of the V heavy chain gene. This differential mutational status of the Ig V gene has significant impact on patient survival. Modern cytogenetic methods such as fluorescence in situ hybridisation (FISH) have opened a new era in the molecular analysis of CLL cells. Determining the chromosomal aberration of the leukaemic cells has become a standard scientific programme for each clinical trial. The cytogenetic profile may soon help to define a clinical risk profile and guide the various treatment strategies. Further progress has been made in the therapy of CLL. Purine analogues such as fludarabine were able to induce significant improvement in remission rates; however, they did not lead to improved survival. Chimera of murine or rat monoclonal antibodies and human antibodies were designed to treat CLL. Antibodies such as rituximab and alemtuzumab (Campath-1H), directed against CD20 and CD52, respectively, appear as attractive alternatives to conventional chemotherapy because of their lack of significant myelotoxicity. Studies using myeloablative chemotherapy followed by autologous or allogeneic stem cell transplantation were initiated with the hope of finding a cure for CLL. In contrast to autologous stem cell transplantation, allogeneic transplants appear to display a plateau of relapse rates. In conclusion, for many years CLL was considered as a chronic haematological malignancy that required only few diagnostic tools and for whom no hope of cure could be offered. The current review focuses on recent improvements in diagnosis and treatment of CLL that have opened a new era in the management of patients with this systemic malignancy.
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PMID:New directions in the diagnosis and treatment of chronic lymphocytic leukaemia. 1269 99

Alemtuzumab (Campath-1H, Ilex Pharmaceuticals, San Antonio, TX) is a humanized monoclonal antibody that recognizes the CD52 antigen expressed on malignant and normal B lymphocytes. It has come to be used therapeutically in B-cell malignancies. Responses are seen in non-Hodgkin's lymphoma (NHL), and alemtuzumab can induce molecular remissions in relapsed chronic lymphocytic leukaemia (CLL), even when refractory to purine analogues. Most studies reveal the responses to be superior in the absence of bulky disease. Infusion-related side effects such as rigors, hypotension, and nausea are reduced by using the subcutaneous route of administration. Infectious complications are the most important toxicity seen and are related to the depletion of normal lymphocytes. The clinical efficacy in combination with both fludarabine and rituximab is under investigation.
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PMID:Alemtuzumab therapy in B-cell lymphoproliferative disorders. 1293 18

The cell surface proteins CD20 and CD52 differ significantly in their structures and are expressed on the majority of B cells. Both circulating CD20 (cCD20) and circulating CD52 (cCD52) have been recently documented in patients with chronic lymphocytic leukaemia. A retrospective study to establish whether cCD20 and/or cCD52 were detectable in patients with lymphoma, and the clinical associations of these soluble antigens if detected, was conducted. cCD20 and cCD52 levels were analysed in a cohort of 65 patients with non-Hodgkin's lymphoma (NHL) and 37 with Hodgkin's disease (HD). Patients with NHL had elevated pretherapy levels of cCD20 and cCD52 compared with normal individuals. Patients with HD had significantly lower than normal pretherapy levels of both cCD20 and cCD52. cCD20 levels were marginally elevated post-therapy in NHL patients while in patients with HD, cCD20 levels remained significantly lower than normal after therapy. Serum cCD52 levels became significantly lower than normal post-therapy in NHL patients, and remained significantly lower than normal in HD patients. No predictive effects were found for pretherapy or post-therapy levels of cCD52 on survival for either cohort of patients. Post-therapy cCD20 levels independently highly correlated with survival in patients with NHL. Prospective evaluation will be required to establish if cCD20 and cCD52 may be used as biomarkers in the diagnosis, prognostic categorization, and monitoring of the clinical course in patients with lymphoma. The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study.
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PMID:Circulating CD20 and CD52 in patients with non-Hodgkin's lymphoma or Hodgkin's disease. 1463 76

After rapid improvement of treatment results in adult acute lymphoblastic leukemia (ALL) from less than 10% to 30-40% in the past decades, more recently stagnation has been observed. In addition, a borderline for further intensification of chemotherapy appears to be reached in adult ALL patients. New, preferably non-chemotherapy, approaches are therefore urgently required. One of those is targeted therapy with monoclonal antibodies (MoAbs). ALL blast cells express a variety of specific antigens which may serve as targets, such as CD19, CD20, CD22, CD33, and CD52. Published results of MoAbs in ALL are reviewed. Most experience is available for anti-CD20 (rituximab) which led to a significant improvement of the outcome in B-cell non-Hodgkin's lymphoma (NHL). In ALL, rituximab is combined with chemotherapy mainly in mature B-ALL and Burkitt's lymphoma and preliminary results are promising. In the future, studies will also be done in B-precursor ALL. Another promising B-cell antibody is anti-CD22. Several CD19 MoAbs were also tested in phase I studies. However, results are not conclusive and these MoAbs are not generally available. Far less experience with MoAb therapy is available for T-ALL, but clinical studies are on the way with anti-CD52 and anti-CD25 in adult T-cell leukemia/lymphoma. Overall, it can be stated that MoAb therapy in ALL is a promising treatment approach. Monotherapy with MoAbs in relapsed ALL occasionally led to responses, but higher effectivity can be expected from a combination with chemotherapy and treatment in the state of minimal residual disease. Well-designed studies and joint efforts are required to explore optimal combinations, timing and dosage of MoAb therapy in ALL.
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PMID:Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. 1464 23

Mouse, chimeric, humanized and human monoclonal antibodies (MABs) are all in use for treatment of human cancer. Unconjugated antibodies have a complex mechanism of action, dependent on the nature of the target structure. Antibodies can activate the immune system (antibody-dependent cellular cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC], induction of tumor immunity [idiotype network]). ADCC appears to be one of the most important immune effector functions. Antibodies may also induce apoptosis, cell cycle arrest, inhibition of cell proliferation as well as angiogenesis and metastatic spread. For most antibodies there is no clear dose-response relationship in vivo. The effect of antibodies can be enhanced by combination with chemotherapy and/or by agents which activate the immune system. The best therapeutic effect may be obtained if MABs are used early in the course of the disease. Rituximab (anti-CD20) was the first registered MAB for the therapy of follicular lymphoma. Impressive results have been seen in combination with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) in follicular and high-grade lymphomas. In other non-Hodgkin's lymphoma subtypes, promising results are also seen in combination with chemotherapy. Trastuzumab (anti-Her2) is a breakthrough in the treatment of breast cancer in combination with chemotherapeutic agents. This antibody is also in clinical testing for adjuvant treatment. Alemtuzumab (anti-CD52) has shown impressive results both in refractory chronic lymphocytic leukemia and as up-front therapy. There are many other antibodies in late stages of testing for registration. Interesting MABs include cetuximab (anti-epidermal growth factor receptor [EGFR]), especially in combination with radiotherapy in head and neck cancer; ABX-EGF (anti-EGFR) in renal carcinoma; bevacizumab (anti-vascular endothelial growth factor) in several solid tumors. Antiepithelial cell adhesion molecule antibodies show promise in combination with chemotherapy in the adjuvant setting of colorectal carcinoma. It is estimated that about 20 antibodies will be in clinical use by the year 2010.
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PMID:Monoclonal antibodies in human cancer. 1498 43


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