Remission Induction in Non-Hodgkin Lymphoma With Reshaped Human Monoclonal Antibody Campath-1h

Hale, Geoff; Clark, Mike; Marcus, Robert; Winter, Gregory; Dyer, Martin J. S.; Phillips, Jenny; Riechmann, Lutz; Waldmann, Herman

doi:10.1016/s0140-6736(88)90588-0

Cited by 531 publications

(157 citation statements)

References 12 publications

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“…The CDw52 antigen is present on virtually all lymphoid cells and at a lower cell-surface density on monocytes and macrophages (21). The antibody has been shown to effectively deplete tissue-infiltrating lymphoid cells in patients with non-Hodgkin's lymphoma (22).…”

Section: Methodsmentioning

confidence: 99%

Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis

Jendro

Ganten

Matteson

et al. 1995

Arthritis & Rheumatism

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Objective. To examine the compartment of CD4+ T cells in patients with rheumatoid arthritis (RA) who have developed persistent lymphopenia following antibody-mediated T cell depletion and to investigate why T cell depletion is of limited therapeutic efficacy.Methods. Circulating T lymphocytes from 10 patients with seropositive RA treated with the monoclonal antibody (MAb) CAMPATH-1H were longitudinally monitored by fluorescence-activated cell sorter analysis with MAb. To assess the molecular diversity of repop ulating T cells, random samples of T cell clones from the peripheral blood of 3 patients were analyzed by sequencing the T cell receptor (TCR) p chains. At the time of recurring disease, the synovial tissue was examined by immunohistochemistry, and the repertoires of peripheral and synovial tissue T cells were compared by TCR P-chain sequencing and by semiquantitative hybridization with oligonucleotides specific for the V-D-JB junctional region of selected clones.Results. The reconstitution of the peripheral T cell compartment was very slow. A mean CD4+ T cell count of 105/pI was reached 34 weeks following MAb treatment. After treatment, the percentage of CD4+ T cells with the CD45RO+ phenotype was significantly increased (P = 0.001), indicating the expansion of antigen-primed memory T cells. TCR &chain sequences revealed a marked restriction in the diversity of repop-

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Section: Methodsmentioning

confidence: 99%

Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis

Jendro

Ganten

Matteson

et al. 1995

Arthritis & Rheumatism

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“…The production of antimouse antibodies can be controlled to some extent by immunosuppressive drugs, for example Cyclosporin A (Ledermann et al, 1988), although general immunosuppression of patients is undesirable. To overcome the problem of immunogenicity of murine antibodies, chimeric antibodies constructed from the variable regions of the mouse antibody together with human constant regions have been produced and have shown reduced immunogenicity in man (LoBuglio et al, 1989), as have humanised antibodies constructed from only the hypervariable complementarity-determining regions (CDRs) of the mouse antibody built into the framework of a human antibody (Hale et al, 1988;Hird et al, 1991).…”

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confidence: 99%

Polyethylene glycol modification of a galactosylated streptavidin clearing agent: effects on immunogenicity and clearance of a biotinylated anti-tumour antibody

Marshall

Pedley²,

Boden³

et al. 1996

Br J Cancer

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Summary Effective radioimmunotherapy is limited by slow antibody clearance from the circulation, which results in low tumour to blood ratios and restricts the dose of radiolabelled anti-tumour antibody that can be safely administered. Avidin and streptavidin clearing agents have been shown to effectively complex and clear radioactive biotinylated antibodies from the circulation, but their immunogenicity may limit their repeated use. We have investigated whether polyethylene glycol (PEG) modification can reduce the immunogenicity of our galactosylated streptavidin (gal-streptavidin) clearing agent without altering its effectiveness as a clearing agent. The immune response evoked in mice after intraperitoneal injection of 30 ,g of gal-streptavidin was decreased after PEG modification, as shown by lower antibody titres and a reduction in the number of mice that elicited an anti-gal-streptavidin response. The effect of PEG-modified gal-streptavidin on the blood clearance and tumour localisation of a "5I-labelled biotinylated anti-CEA was investigated in the LS174T human colon carcinoma xenograft in nude mice. Although PEG modified gal-streptavidin bound the ['25I]biotinylated antibody in vivo, effective clearance from the circulation was inhibited, resulting in very little reduction in the levels of circulating radioactivity, together with a decrease in the antibody localised to the tumour.

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“…15 Although alemtuzumab has been approved only for the treatment of lymphoid neoplasias, it has been used, due to its mechanism of action, after renal transplantation and autoimmune diseases, such as rheumatoid arthritis, vasculites, and multiple sclerosis. 16,17 Similarly to thymoglobulin, the administration dosage of alemtuzumab is varied, and doses of 20 to 30 mg, in single or fractioned infusion, in the perioperative period are the most commonly used.…”

Section: Definitionsmentioning

confidence: 99%

Terapia de indução com alentuzumabe em receptores de transplante renal

Sampaio¹,

Freitas²,

Galante³

et al. 2010

J. Bras. Nefrol.

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Introduction: Induction therapy has been used in sensitized patients, re-transplants, and in patients who have high risk to delayed graft function (DGF) after renal transplantation. Methods: Retrospective study with aim to compare transplant endpoints between recipients of deceased donors which have received induction with alemtuzumab (n = 9) versus thymoglobulin (n = 18). Patients were matched for age, duration of dialysis treatment and cold ischemia time. Results: There were no differences at demographic characteristics. All patients received kidney grafts from deceased donors and 67% of these donors met the expanded criteria. The incidence of DFG was similar in alemtuzumab and thymoglobulin groups, 55% and 56%. At 12 months, rates of rejection free survival (67% versus 89%, p = 0,13), graft survival (62,5% versus 76,6%; p = 0,73), graft with death censored (62,5% versus 76,6%; p = 0,82) and patient survival (83,3% versus 81,2%; p = 0,63) were similar between the two groups. Viral infections and renal function were similar between groups. At the end of the first month, alemtuzumab patients displayed a fewer lymphocyte number (135 ± 78 versus 263 ± 112 N/mm 3 , p < 0,05) followed by a more rapid recovery after 3 months (day 90: 683 ± 367 versus 282 ± 72 N/mm 3 ; p < 0,05). Cost associated with alemtuzumab and thymoglobulin inductions therapies were R$ 1,388.00 and R$ 7,398.00. Conclusion: In this cohort of patients, alemtuzumab induction showed efficacy and safety comparable to thymoglobulin but with significant cost reduction.

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Remission Induction in Non-Hodgkin Lymphoma With Reshaped Human Monoclonal Antibody Campath-1h

Cited by 531 publications

References 12 publications

Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis

Emergence of oligoclonal t cell populations following therapeutic t cell depletion in rheumatoid arthritis

Polyethylene glycol modification of a galactosylated streptavidin clearing agent: effects on immunogenicity and clearance of a biotinylated anti-tumour antibody

Terapia de indução com alentuzumabe em receptores de transplante renal

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