Side Effects and Immunogenicity of Murine Lymphocyte-Specific Monoclonal Antibodies in Subhuman Primates

Jonker, Margreet; Nooij, F. J. M.; Butter, G. Den; Lambalgen, R. Van; Fuccello, Anthony

doi:10.1097/00007890-198804000-00002

Cited by 15 publications

(4 citation statements)

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“…the numbers in the table suggest several observations: For example, experiments in the most recent decade (2001-10) generally used smaller numbers of chimpanzees than in the previ- observe infusion reactions following their administration (Van Meurs and Jonker, 1986;Jonker et al, 1988). In the 1990's, many published articles on mAb studies with chimpanzees continued to focus on properties of the serum and the immune response.…”

Section: Number Of Chimpanzees In a Given Experimentsmentioning

confidence: 99%

Systematic review of chimpanzee use in monoclonal antibody research and drug development: 1981-2010

Bettauer

2011

ALTEX

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Section: Number Of Chimpanzees In a Given Experimentsmentioning

confidence: 99%

Systematic review of chimpanzee use in monoclonal antibody research and drug development: 1981-2010

Bettauer

2011

ALTEX

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“…Using the 2-ME method, a high labelling efficiency of 90% and specific activity of 110.2 mCi/mg was obtained (unpublished data). 1D09C3 is a fully humanised IgG 4 monoclonal antibody and does not induce Fc-portion-mediated side effects, like chimeric antibodies do (Billing and Chatterjee, 1983;Jonker et al, 1988). Studies demonstrated that 1D09C3 has in vivo as well as in vitro tumoricidal activity and it can act selectively on tumor-transformed and activated cells via a non-apoptotic mechanism (Nagy et al, 2002).…”

Section: Anti-dr Antibodymentioning

confidence: 99%

Radiopharmaceuticals for imaging chronic lymphocytic inflammation

Malviya

Vries

Dierckx

et al. 2007

Braz. arch. biol. technol.

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In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the preclinical diagnosis of chronic inflammatory processes, even before anatomical and functional changes occur in affected tissues. Moreover, the introduction of radiolabelled monoclonal antibodies and sophisticated technique like PET/CT now make the field of inflammationimaging highly specific and accurate. In this review, different approaches of the established and experimental radiopharmaceuticals for imaging of chronic inflammation are discussed.

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“…IgG4 antibodies differ functionally from other IgG subclasses by their poor ability to stimulate the complement system thus minimizing side effects due to Fc-portion-mediated effector functions [12, 13]. Studies showed its in vivo as well as in vitro tumouricidal activity and described that it acts selectively on tumour-transformed and activated cells via a non-apoptotic mechanism [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 99mTc-Labelled Monoclonal Antibody 1D09C3 for Molecular Imaging of Major Histocompatibility Complex Class II Protein Expression

2010

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PurposeIt is known that major histocompatibility complex class II protein HLA-DR is highly expressed in B-cell lymphomas and in a variety of autoimmune and inflammatory diseases. Therefore, a radiolabelled fully humanized IgG4 monoclonal antibody (mAb) can provide useful prognostic and diagnostic information. Aims of the present study were to radiolabel an anti-HLA-DR mAb with technetium-99m and to evaluate its binding specificity, tissue distribution and targeting potential.ProceduresFor labelling, we compared a direct method, after 2-mercaptoethanol (2-ME) reduction of disulphide bonds, with a two-step labelling method, using a heterobifunctional succinimidyl-6-hydrazinonicotinate hydrochloride chelator. Several in vitro quality controls and in vivo experiments in mice were performed.ResultsWe obtained highest labelling efficiency (LE, >98%) and specific activity (SA; 5,550 MBq/mg) via the direct method. In vitro quality control showed good stability, structural integrity and retention of the binding properties of the labelled mAb. The biodistribution in mice showed high and persistent uptake in spleen and suggests kidney and liver-mediated clearance pathways. In tumour targeting experiments, we observed high uptake in HLA-DR-positive xenografts compared to controls. In vivo binding was proportional to the number of injected cells. In the in vivo blocking assay, uptake of radiolabelled mAb was significantly decreased in mice pre-injected with 100-fold molar excess of unlabelled mAb.ConclusionWe efficiently labelled a humanized anti-HLA-DR mAb with 99mTc using a direct labelling method. Radiolabelled mAb binds to human HLA-DR antigens and therefore warrants further evaluation as a prognostic and diagnostic tool for patients with lymphoma or autoimmune diseases.

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Side Effects and Immunogenicity of Murine Lymphocyte-Specific Monoclonal Antibodies in Subhuman Primates

Cited by 15 publications

References 0 publications

Systematic review of chimpanzee use in monoclonal antibody research and drug development: 1981-2010

Systematic review of chimpanzee use in monoclonal antibody research and drug development: 1981-2010

Radiopharmaceuticals for imaging chronic lymphocytic inflammation

Synthesis and Evaluation of 99mTc-Labelled Monoclonal Antibody 1D09C3 for Molecular Imaging of Major Histocompatibility Complex Class II Protein Expression

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