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)

Antiserum was generated in rabbits to the RPMI 8226 tissue culture line of human myeloma cells, and its reactions with fixed smears of bone marrow aspirates from patients with multiple myeloma, macroglobulinemia, benign monoclonal gammopathy (BMG), leukemia, and nonneoplastic plasmacyosis was assessed by indirect immunofluorescence. After absorption with preparations of bone marrow from normal individuals, the antiserum reacted to a significantly higher titer with a specific subpopulation of plasma cells in smears from 81% of patients having multiple myeloma and 50% of patients having BMG than with cells in smears of bone marrow aspirates from normal individuals or patients having leukemia or nonneoplastic plasmacytosis, or than with cells in smears of peripheral blood from patients having Hodgkin's and non-Hodgkin's lymphoma. Absorption of the antiserum with RPMI 8226 cells or with a bone marrow preparation from a patient with multiple myeloma but not the Jijoye line of Burkitt's lymphoma reduced reactivity for cells in myeloma bone marrow. The antiserum reacted at a lower titer with the Jijoye and EB-3 lines of Burkitt's lymphoma, the RPMI 4098 cell line of normal human lymphocytes, and culture lines of human melanoma and osteogenic sarcoma than with the RPMI 8226 cells or bone marrow from certain patients having multiple myeloma. Approximately 50% of the cells reactive with antiserum to RPMI 8226 cells in the bone marrow of patients with multiple myeloma were not producing immunoglobulin, as assessed by double immunofluorescence assay. The data suggested that a subpopulation of plasma cells in the bone marrow of patients with multiple myeloma possesses a tumor-associated antigen.
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PMID:Tumor-associated antigens in human myeloma. 5 51

Pretargeted radioimmunotherapy (PRIT) was first investigated in a series of phase I and phase II studies in patients with adenocarcinoma using a pancarcinoma antibody, NR-LU-10. The principles and schema developed were then applied to an initial study in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor-associated antigen receptor, and subsequently, biotin is used to target the 90Y radioisotope to the tumor localized streptavidin. In the NHL study, a chimeric, IgG1, anti-CD20 antibody (Rituximab) was conjugated to streptavidin (SA) and administered to patients. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied, and seven received 30 or 50 mCi/m(2) 90Y DOTA-biotin. Preliminary studies using 186Re labeled conjugate confirmed that it localized to tumor and that the clearing agent removed >95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29+/-23 cGy/mCi 90Y, and the mean tumor to whole body dose ratio was 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e. five of the seven patients who received 30 or 50 mCi/m(2) of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of 10 patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m(2) 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than that achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.
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PMID:Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma (NHL). 1157 15

Pretargeted radioimmunotherapy (PRIT) decreases the amount of time that radioactivity non-selectively circulates. Our PRIT approach is a multi-step method in which a monoclonal antibody is used to target streptavidin to a tumor-associated antigen and biotin is then used to target 90Y to the streptavidin. A genetically engineered antibody streptavidin fusion construct was used to target tumor in a patient with non-Hodgkin's lymphoma. Impressive localization of 90Y to known and previously unknown areas of adenopathy was observed, thus demonstrating that a genetically engineered fusion protein can selectively target lymphoma cells as part of a clinically meaningful PRIT strategy.
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PMID:Pretargeted radioimmunotherapy (PRIT) using an antibody-streptavidin fusion protein in non-Hodgkin's lymphoma. 1248 94

Antibody-drug conjugates (ADCs) are a broad class of molecules comprising of a potent cytotoxic agent conjugated with a monoclonal antibody using a chemically stable linker. By selecting a monoclonal antibody directed against a tumor-specific or tumor-associated antigen, ADCs allow the targeted delivery of highly potent cytotoxic agents that result in unacceptable toxicity when administered as free agents. ADCs are currently being developed for the treatment of a wide variety of tumors. In this review, the current clinical and preclinical status of ADCs for the treatment of B-cell non-Hodgkin's lymphoma and B-cell leukemia will be discussed. ADCs have the potential to alter treatment paradigms for these diseases by providing both increased efficacy and improved safety and tolerability over current chemotherapy-based regimens.
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PMID:Antibody-drug conjugates for the treatment of B-cell non-Hodgkin's lymphoma and leukemia. 2346 71