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)

LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high sensitivity for detecting B-cell, non-Hodgkin's lymphoma (NHL), as well as an antitumor efficacy in therapeutic applications. The aim of this study was to determine whether intracellularly retained radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro studies showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from the cell. In contrast, residualizing radiolabels, such as radioactive metals, are retained intracellularly for substantially longer. In vivo studies were performed using LL2-labeled with radioiodine by a non-residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine, DLT), or with a radioactive metal (111In). The biodistribution of a mixture of 125I (non-residualizing chloramine-T compared to residualizing DLT), 111In-labeled LL2 murine IgG2a or its fragments [F(ab')2, Fab'], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell NHL cell line. Radiation doses were calculated from the biodistribution data according to the Medical International Radiation Dose scheme to assess the potential advantage for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing labels (i.e., 111In and DLT-125I) than with the non-residualizing iodine label. For example, tumor/blood ratios of 111In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ ratios also were higher with residualizing labels. No significant differences in tumor, blood and organ uptake were observed between murine and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values comparable to those of iodinated LL2, the uptake of both antibodies being strongly dependent on tumor size. These data suggest that, with internalizing antibodies such as LL2, labeling with intracellularly retained isotopes has an advantage over released ones, which justifies further clinical trials with residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and 90Y labels for therapy.
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PMID:Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma antigen, CD22. 919 78

Pralatrexate, a 10-deazaaminopterin derivative, is being developed by Allos Therapeutics Inc for the potential treatment of malignancies. The folate analog inhibits dihydrofolate reductase and was developed to overcome the limitations of the folate analog methotrexate. Compared with methotrexate in preclinical studies, pralatrexate demonstrated superior intracellular transport via the reduced folate carrier, and increased accumulation within cells by enhanced polyglutamylation. Preclinical studies in vitro and in models of B-cell lymphomas, T-cell lymphomas and NSCLC indicated that pralatrexate exhibited antitumor activity that was superior to the activity of other antifolates. In phase I clinical trials, the DLT for pralatrexate was mucositis, which could be abrogated with folic acid and vitamin B12 supplementation. The administration of pralatrexate to patients with T-cell lymphomas and NSCLC resulted in significant tumor remissions. At the time of publication, pralatrexate was in phase II clinical trials for the treatment of peripheral T-cell lymphoma, a phase I/II trial in combination with gemcitabine for the treatment of non-Hodgkin's lymphoma, and a phase IIb trial in comparison with erlotinib in patients with NSCLC. Because of the limited therapies available for peripheral T-cell lymphoma, pralatrexate could have a secure niche for the treatment of this indication, if ongoing clinical trials and future phase III trials confirm the efficacy of the drug. In contrast, for pralatrexate to be incorporated into the accepted treatment options for NSCLC, the drug will need to prove clear superiority to established agents.
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PMID:Pralatrexate, a dihydrofolate reductase inhibitor for the potential treatment of several malignancies. 1860 May 98