Guidelines for the welfare and use of animals in cancer research

Workman, Paul; Aboagye, Eric O.; Balkwill, Frances R.; Balmain, Allan; Bruder, Greg; Dj, Chaplin; Double, J A; Everitt, Jeffrey I.; Farningham, D.A.H.; Glennie, M J; Kèlland, Lloyd R.; Robinson, Vicky; Stratford, Ian J.; Tozer, Gillian M.; Watson, Sue‐Ann; Wedge, Stephen R.; Eccles, Sue; Navaratnam, V.; Ryder, Stephen D.

doi:10.1038/sj.bjc.6605642

Cited by 1,213 publications

(1,068 citation statements)

References 186 publications

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“…All experiments were conducted in accordance with the UK Home Office Animals (Scientific Procedures) Act 1986, with local ethical approval and recently published guidelines. 71 …”

Section: Methodsmentioning

confidence: 99%

“…Studies were conducted by Covance Laboratories Ltd, UK, in accordance with the requirements of the United Kingdom Home Office Animals (Scientific Procedures) Act 1986, with local ethical approval and recently published guidelines. 71 All procedures in the study were also in compliance with the German Animal Welfare Act (1972), were approved by the local Institutional Animal Care and Use Committee, and in consideration of European Commission Recommendation 2007/526/EC on guidelines for the accommodation and care of animals used for experimental and other scientific purposes (Appendix A of Convention ETS 123).…”

Section: Methodsmentioning

confidence: 99%

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Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Smith

Kießling

Lledó-García

et al. 2018

mAbs

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Rozanolixizumab (UCB7665), a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P), has been developed to reduce pathogenic IgG in autoimmune and alloimmune diseases. We document the antibody isolation and compare rozanolixizumab with the same variable region expressed in various mono-, bi- and trivalent formats. We report activity data for rozanolixizumab and the different molecular formats in human cells, FcRn-transgenic mice, and cynomolgus monkeys. Rozanolixizumab, considered the most effective molecular format, dose-dependently and selectively reduced plasma IgG concentrations in an FcRn-transgenic mouse model (no effect on albumin). Intravenous (IV) rozanolixizumab dosing in cynomolgus monkeys demonstrated non-linear pharmacokinetics indicative of target-mediated drug disposition; single IV rozanolixizumab doses (30 mg/kg) in cynomolgus monkeys reduced plasma IgG concentration by 69% by Day 7 post-administration. Daily IV administration of rozanolixizumab (initial 30 mg/kg loading dose; 5 mg/kg daily thereafter) reduced plasma IgG concentrations in all cynomolgus monkeys, with low concentrations maintained throughout the treatment period (42 days). In a 13-week toxicology study in cynomolgus monkeys, supra-pharmacological subcutaneous and IV doses of rozanolixizumab (≤ 150 mg/kg every 3 days) were well tolerated, inducing sustained (but reversible) reductions in IgG concentrations by up to 85%, with no adverse events observed. We have demonstrated accelerated natural catabolism of IgG through inhibition of IgG:FcRn interactions in mice and cynomolgus monkeys. Inhibition of FcRn with rozanolixizumab may provide a novel therapeutic approach to reduce pathogenic IgG in human autoimmune disease. Rozanolixizumab is being investigated in patients with immune thrombocytopenia (NCT02718716) and myasthenia gravis (NCT03052751).

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“…All experiments were conducted in accordance with the UK Home Office Animals (Scientific Procedures) Act 1986, with local ethical approval and recently published guidelines. 71 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Smith

Kießling

Lledó-García

et al. 2018

mAbs

View full text Add to dashboard Cite

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“…Animal care and experiments were in accordance with Institutional guidelines and the indications of Workman et al 29 …”

Section: Cells and Animalsmentioning

confidence: 99%

Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models

et al. 2015

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The multifaceted immunomodulatory activity of DNA hypomethylating agents improves immunogenicity and immune recognition of neoplastic cells; thus, we predicted they could be utilized to design new immunotherapeutic combinations in cancer. Testing this hypothesis, the antitumor efficacy of the DNA hypomethylating agent 5-aza-2 0 -deoxycytidine (5-AZA-CdR) combined with the anti-CTLA-4 monoclonal antibody (mAb) 9H10 in syngeneic transplantable murine models was investigated. Murine mammary carcinoma TS/A or mesothelioma AB1 cells were injected in BALB/c, athymic nude, and SCID/Beige mice that were treated with 5-AZA-CdR, mAb 9H10, or their combination. Tumor volumes were captured at different time-points; molecular and immunohistochemical assays investigated changes in neoplastic and normal tissues. A significant antitumor effect of 5-AZA-CdR combined with mAb 9H10 was found: compared to controls, a 77% (p < 0.01), 54% (p < 0.01) and 33% (p D 0.2) decrease in TS/A tumor growth was induced by 5-AZA-CdR combined with mAb 9H10, 5-AZA-CdR or mAb 9H10, respectively. These antitumor activities were confirmed utilizing the AB1 model. 5-AZA-CdR-based regimens induced a promoter-demethylationsustained tumor expression of cancer testis antigens. MHC class I expression was up-regulated by 5-AZA-CdR. Antitumor efficacy of 5-AZA-CdR in athymic nude and SCID/Beige mice was not increased by mAb 9H10. In BALB/c mice, combined treatment induced the highest tumor infiltration by CD3 C lymphocytes, which included both CD8 C and CD4 C T cells; no such infiltrates were observed in normal tissues. This significant immune-related antitumor activity of 5-AZA-CdR combined with CTLA-4 blockade, demonstrated in highly aggressive mouse tumor models, provides a strong scientific rationale to implement epigenetically-based immunotherapies in cancer patients.

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“…All animal experiments were conducted in accordance with the United Kingdom Home Office Animals (Scientific Procedures) Act 1986, with local ethical approval and in line with recently published Guidelines for the Welfare of Animals in Cancer Research (Workman et al, 2010). Surgical procedures were as described previously (Tozer et al, 2005a).…”

Section: Methodsmentioning

confidence: 99%

Online chromatic and scale-space microvessel-tracing analysis for transmitted light optical images

Reyes-Aldasoro

Björndahl

Akerman

et al. 2012

Microvascular Research

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This is the unspecified version of the paper.This version of the publication may differ from the final published version. Permanent repository link AbstractLimited contrast in transmitted light optical images from intravital microscopy is problematic for analysing tumour vascular morphology. Moreover, in some cases, changes in vasculature are visible to a human observer but are not easy to quantify. In this paper two online algorithms are presented: scalespace vessel tracing and chromatic decomposition for analysis of the vasculature of SW1222 human colorectal carcinoma xenografts growing in dorsal skin-fold "window" chambers in mice. Transmitted light optical images of tumours were obtained from mice treated with the tumour vascular disrupting agent, combretastatin-A-4-phosphate (CA4P), or saline. The tracing algorithm was validated against hand-traced vessels with accurate results. The measurements extracted with the algorithms confirmed the known effects of CA4P on tumour vascular topology. Furthermore, changes in the chromaticity suggest a deoxygenation of the blood with a recovery to initial levels in CA4P-treated tumours relative to the controls. The algorithms can be freely applied to other studies through the CAIMAN website (CAncer IMage ANalysis: http://www.caiman.org.uk).

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Guidelines for the welfare and use of animals in cancer research

Cited by 1,213 publications

References 186 publications

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models

Online chromatic and scale-space microvessel-tracing analysis for transmitted light optical images

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