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

CD22 is a 135-kd B-cell restricted sialoglycoprotein present in the cytoplasm of virtually all B-lineage cells but expressed on the B-cell surface only at mature stages of differentiation. In humans, the vast majority of IgM(+)IgD(+) B cells express cell-surface CD22, while in lymphoid tissues CD22 expression is high in follicular mantle and marginal zone B cells and weak in germinal center B cells. In B-cell malignancies, CD22 expression ranges from 60% to 80% depending on the histological type and on the assays used. The function of the CD22 molecule is uncertain, although recent studies have suggested roles for the molecule both as a component of the B-cell activation complex and as an adhesion molecule. CD22-deficient mice have a reduced number of mature B cells in the bone marrow and circulation; the B cells have a shorter lifespan and enhanced apoptosis, thus indicating a key role of this antigen in B-cell development/survival. After binding with its natural ligand(s) or antibodies, CD22 is rapidly internalized; this provides a potent costimulatory signal in primary B-cell and proapoptotic signals in neoplastic B cells. Preclinically CD22 has been shown to be an effective target for immunotherapy of B-cell malignancies using either "naked" or toxin-labeled or radiolabeled monoclonal antibodies. Clinical trials in patients with non-Hodgkin's lymphoma (NHL) (both indolent and aggressive disease) are now ongoing with a humanized naked anti-CD22 antibody (epratuzumab, Amgen Inc, thousand Oaks, CA and Immunomedics Inc, Morris Plains, NJ) used as single agent or in combination with other monclonal antibodies (ie, rituximab) and/or chemotherapy. Preliminary data from these studies showed these approaches to be effective and well-tolerated.
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PMID:CD22 as a target of passive immunotherapy. 1272 Jan 47

Immunomedics and Amgen are developing the unconjugated form of the anti-CD22 humanized monoclonal antibody, epratuzumab, for the potential treatment of lymphoma, non-Hodgkin's lymphoma (NHL) and certain autoimmune conditions. Immunogenics is also developing the radioisotope-linked (90Y) form of epratuzumab. The monoclonal antibody is currently undergoing phase III clinical trials for the potential treatment of aggressive lymphoma. By January 2003, epratuzumab had received Orphan Drug status in the US for its potential in the treatment of NHL.
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PMID:Technology evaluation: epratuzumab, Immunomedics/Amgen. 1277 11

Ibritumomab tiuxetan is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy-refractory CD20+ B-cell non-Hodgkin's lymphoma. Whereas chemotherapy agents can successfully be used multiple times in a given patient, there are few data on the repeated use of radioimmunotherapy in terms of efficacy or morbidity, and no reports as yet involving radioconjugates that target different antigens We report on a patient who was treated successfully with yttrium-90-labeled humanized anti-CD22 monoclonal antibody (90Y-epratuzumab). Upon relapse 3 years later, the patient was treated again with radioimmunotherapy consisting of 90Y-ibritumomab tiuxetan anti-CD20 monoclonal antibody, with a good response and acceptable bone marrow suppression. This case report demonstrates the potential for repeated treatments with radioimmunotherapy agents in patients with chemotherapy-refractory non-Hodgkin's lymphoma.
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PMID:Use of ibritumomab tiuxetan anti-CD20 radioimmunotherapy in a non-Hodgkin's lymphoma patient previously treated with a yttrium-90-labeled anti-CD22 monoclonal antibody. 1283 57

Immunotherapy directed against the CD20 antigen has had a profound impact on the management of patients with B-cell non-Hodgkin's lymphoma (NHL). Antibody-based treatments offer a favorable side effect profile, as well as alternate mechanisms of action that may complement those of cytotoxic modalities. Targeting other antigens, such as CD22, may also result in antilymphoma effects. This B-cell-specific molecule is widely expressed in NHL and mediates important functions in B-cell biology. Preclinical and early clinical data suggest that epratuzumab, a humanized anti-CD22 monoclonal antibody, demonstrates antilymphoma effects in both unlabeled and radiolabeled forms, as well as a favorable safety profile. Ongoing and future studies will further determine the role of epratuzumab among the array of antilymphoma therapies, both as a single agent and in combination with other agents.
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PMID:CD22-directed monoclonal antibody therapy for lymphoma. 1293 14

The development of effective B cell-directed monoclonal antibody therapies has dramatically altered the management of patients with B-cell non-Hodgkin's lymphoma. Anti-CD20 murine and chimeric antibodies have been characterized by manageable toxicity profiles and appear to have mechanisms which may be distinct from and complementary to those of chemotherapy. There is considerable rationale for treatment strategies which target other B-cell antigens, including CD22. This molecule is commonly expressed in non-Hodgkin's lymphoma and may mediate important functions in B-cell biology. Laboratory and initial clinical studies suggest that epratuzumab, a humanized anti-CD22 monoclonal antibody, may have antilymphoma activity in both unlabeled and radiolabeled forms. Efforts are underway to establish the utility of epratuzumab as a treatment for B-cell malignancies, through single agent and combination regimens, to define the optimal settings for its clinical application.
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PMID:Epratuzumab: targeting B-cell malignancies through CD22. 1450 98

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

New therapies for chronic lymphocytic leukemia (CLL) are moving away from non-specific cytotoxic to more targeted approaches. The monoclonal antibody alemtuzumab induces responses in 33% to 43% of patients with relapsed or refractory disease, with 2-5% CR. Side effects include infusional reactions as well as immunosuppressive effects. Rituximab has limited activity in relapsed refractory patients, but response rates are comparable to follicular non-Hodgkin's lymphoma in untreated patients. Other antibodies in early phases of development include anti-CD23 [IDEC-152], anti-CD22 [epratuzumab], Hu1D10 [apolizumab], and anti-CD80 [anti-B7, IDEC-114]. Other agents that are being studied include denileukin diftitox fusion protein (Ontak), and bcl-2 antisense [G3139, Genasense]. The mechanism of action of the new drugs and their role in CLL, as well as the emergence of new prognostic markers are discussed.
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PMID:Novel therapies for chronic lymphocytic leukemia. 1501 Jan 51

The field of radioimmunotherapy for the treatment of non-Hodgkin's lymphoma (NHL) has advanced significantly over the past decade, and several radioimmunoconjugates are being tested in clinical trials. Two of these antibodies target CD20: yttrium-90 (Y-90)-labeled ibritumomab tiuxetan (Zevalin) and tositumomab/iodine-131 (I-131)-labeled tositumomab (Bexxar). Other agents target either CD22 (Y-90 epratuzumab) or human leukocyte antigen (HLA)-DR (I-131 Lym-1), respectively. In February 2002, Y-90-labeled ibritumomab tiuxetan became the first radioimmunoconjugate to be approved by the US Food and Drug Administration (FDA) for the treatment of cancer. Tositumomab/I-131 tositumomab was approved in June 2003. Thus, two radioimmunoconjugates have been approved for the treatment of NHL. Both agents, when administered as a single dose, have produced impressive tumor response rates with an acceptable toxicity profile. The main side effect is reversible myelosuppression. Radioimmunotherapy produces overall response rates of approximately 80% in patients with low-grade lymphomas, and 25% to 30% of patients achieve a complete remission. Lower response rates (approximately 40%) have been reported in patients with large-cell lymphomas. This review discusses the clinical trials of radioimmunotherapeutic agents for NHL that demonstrated their safety and efficacy and outlines the current status of these agents.
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PMID:Radioimmunotherapy: a new treatment modality for B-cell non-Hodgkin's lymphoma. 1520 90

Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin's lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.
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PMID:Very late central nervous system relapse in a patient with B cell lymphoblastic lymphoma. 1556 34

Paraffin-embedded diagnostic biopsy materials from a large cohort of pediatric and adolescent patients with mature B-cell non-Hodgkin's lymphoma (NHL) treated on the Children's Cancer Group arm of an international cooperative trial were studied to determine their phenotypic features and the feasibility of using targeted bioimmune therapies. There were 345 patients eligible for analysis: 208 with Burkitt's lymphoma (BL), 43 with high-grade B-cell lymphoma, Burkitt-like (HGBL), and 94 with diffuse large B-cell lymphoma (DLBCL). Samples were immunophenotyped centrally using a standard panel that included CD20, CD79a, CD3, and CD45RO. Additional staining with CD22 was performed on a subset of cases. Immunophenotypic studies showed positive staining with CD20 in 100% of cases of BL and HGBL and in 98% of cases with DLBCL. CD22 expression was present in all cases of BL and DLBCL and in 87% of cases HGBL. This study indicates that immune-based therapies such as rituximab and ibritumomab-tiuxetan (anti-CD20) and epratuzumab (anti-CD22) are feasible in pediatric cases of mature B-cell NHLs.
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PMID:B-Cell non-Hodgkin's lymphoma in children and adolescents: surface antigen expression and clinical implications for future targeted bioimmune therapy: a children's cancer group report. 1622 29


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