Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20
TL;DR: In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity and the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.
About: This article is published in Blood.The article was published on 1994-01-15 and is currently open access. It has received 2112 citations till now. The article focuses on the topics: Murine Monoclonal Antibody 2B8 & Antibody.
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TL;DR: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy, and further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
Abstract: PURPOSEThe CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies.PATIENTS AND METHODSThis was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses.RESULTSFrom 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fe...
2,817 citations
TL;DR: A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks and provides evidence of B-cell involvement in the pathophysiology of relapsing-remitting multiple sclerosis.
Abstract: Background There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes. Methods In a phase 2, double-blind, 48-week trial involving 104 patients with relapsing–remitting multiple sclerosis, we assigned 69 patients to receive 1000 mg of intravenous rituximab and 35 patients to receive placebo on days 1 and 15. The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12, 16, 20, and 24. Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse. Results As compared with patients who received placebo, patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P<0.001) and of total new gadolinium-enhancing lesions over the same period (P<0.001); th...
2,097 citations
TL;DR: This study showed an association between the FCGR3A genotype and clinical and molecular responses to rituximab, and will certainly give rise to new pharmacogenetic approaches to the management of patients with non-Hodgkin lymphomas.
2,000 citations
TL;DR: Likelihood of tumor response was associated with a follicular histology, with the ability to sustain a high serum level of antibody after the first infusion, and with a longer duration of remission to prior chemotherapy, and IDEC-C2B8 has a better safety profile.
1,630 citations
Patent•
14 Jan 2000TL;DR: In this article, the present invention concerns polypeptides comprising a variant of the Fc region, which have altered effector function as a consequence of one or more amino acid modifications in the region thereof.
Abstract: The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.
1,596 citations
References
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TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
65,881 citations
TL;DR: The identification of such a cell line, Sp2/0-Ag14, is reported here the identification of a tumour cell fusion partner that makes no Ig but which can nevertheless be fused with spleen cells to obtain hybrids secreting only the specific antibody.
Abstract: FUSION of myeloma cells which grow in tissue culture with spleen cells from an immunised mouse provides a general method for obtaining cell lines (hybridomas) which make antibody of the desired specificity1–3. Hybrids derived from these myelomas make the immunoglobulin (Ig) heavy and light chains of the myeloma parent as well as the antigen-specific heavy and light chains of the spleen cell parent. In conditions in which the two heavy and two light chains associate randomly, a hybridoma would make 10 distinct Ig molecules, and the specific antibody would comprise only 1/16 of the total Ig4,5. To obtain hybridomas making only the specific antibodies requires a tumour cell fusion partner that itself makes no Ig but which can nevertheless be fused with spleen cells to obtain hybrids secreting only the specific antibody. We report here the identification of such a cell line, Sp2/0-Ag14.
1,654 citations
Journal Article•
TL;DR: The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51Cr) or loss of cloning efficiency.
Abstract: The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51Cr) or loss of cloning efficiency. When sensitized lymphoid cells were incubated with target cells at a ratio of 100:1, up to 90 per cent of the incorporated label was released within 6–9 hours, while the number of clone-forming cells was reduced by up to 99 per cent in the same time period. Isoantiserum from the graft recipients, as well as its 19S and 7S fractions, protected target cells against the toxic effect of the spleen cells, but a lipoprotein antigen isolated from the tumour cells failed to inhibit the cytotoxic reaction. Target cell lysis as measured by specific release of 51Cr was partially inhibited by actinomycin-D and by cycloheximide at concentrations which effectively blocked DNA-dependent RNA and protein synthesis.
1,329 citations
TL;DR: A new dominant hybrid genetic marker, suitable for selection in higher eukaryotic cells, has been obtained by linking the promoter region of the Herpes simplex virus type I thymidine kinase gene to the gene coding for the aminoglycoside 3′ phosphotransferase coded for by the Tn5 transposon.
859 citations