An inter-laboratory retrospective analysis of immunotoxicological endpoints in non-human primates: T-cell-dependent antibody responses

Lebrec, Hervé; Cowan, Laine A.; Lagrou, Michelle; Krejsa, Cecile M.; Neradilek, Moni B.; Polissar, Nayak L.; Black, Lauren E.; Bussiere, Jeanine L.

doi:10.3109/1547691x.2011.587473

Cited by 26 publications

(9 citation statements)

References 4 publications

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“…However, the 2C1.1 treated group did not show a statistically significant difference from the DNP-IgG 2 control. It would require group sizes of at least 12 animals to achieve sufficient statistical power to distinguish the differences observed here, given the large variation in animal responses to immunization, variations which are consistent with previous observations around the variability of TDAR assay responses in non-human primates (Lebrec et al, 2011). It should be noted that the study design was powered with the expectation that there would be an inhibitory effect similar to that of CsA given the similar level of IL-2 inhibition observed with both molecules.…”

Section: C11 Fails To Block the Primary Immune Response To Srbcsupporting

confidence: 69%

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Gaida¹,

Salimi-Moosavi²,

Subramanian³

et al. 2014

Journal of Immunotoxicology

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(2015) Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey, Journal of Immunotoxicology, 12:2,[164][165][166][167][168][169][170][171][172][173] RESEARCH ARTICLEInhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey 2+ entry induces proliferation and cytokine production through activation of calcineurin and the nuclear factor of activated T-cells (NFAT) transcription factor along with subsequent cytokine-related genes. It was hypothesized that the in vivo inhibition of T-cell function by blocking ORAI1 or calcineurin would lead to similar functional consequences. To test this hypothesis the activity of 2C1.1, a fully human anti-ORAI1 monoclonal antibody, and cyclosporin A (CsA) were tested in vivo for their suppressive effect on T-cell-derived cytokine production and a T-cell-dependent antibody response (TDAR) using sheep red blood cells (SRBC) in cynomolgus monkeys. Despite showing similar inhibition of ex vivo interleukin (IL)-2 production by stimulated T-cells, both molecules exhibited different pharmacologic effects on the SRBC antibody response. CsA blocked the development of SRBC-specific antibodies, while 2C1.1 failed to inhibit the antigen-specific antibody response. These surprising observations suggest that full inhibition of the CRAC channel is required to inhibit a functional immune response, consistent with findings from human patients with loss of function mutations in ORAI1.

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Section: C11 Fails To Block the Primary Immune Response To Srbcsupporting

confidence: 69%

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Gaida¹,

Salimi-Moosavi²,

Subramanian³

et al. 2014

Journal of Immunotoxicology

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“…This recommendation is driven by having infants of either appropriate body size for blood volume collection or a maturation status that allows for learning and memory testing. With regard to animal number, there are reports that a group size of eight animals for TDAR (Lebrec et al, 2011) and a group size of six to eight animals for lymphocyte immunophenotyping (Krejsa et al, 2013) pro-vide acceptable statistical power for detecting alterations. It has also been demonstrated for learning and memory testing in juvenile animals that a group size of eight animals yields sufficient statistical power (Rose et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (<i>Macaca fascicularis</i>)

et al. 2020

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Abstract. Enhanced pre- and postnatal development (ePPND) studies have become the default developmental toxicity test for biopharmaceuticals if nonhuman primates represent the relevant species. Spontaneous pregnancy losses and infant deaths can be significant in macaques such as long-tailed macaques. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline S6(R1) states that pregnancy outcome can be judged also by the normogram-based variability of reference data according to a publication by Jarvis et al. (2010) defining a study as valid with six to eight live infants in the control group on postnatal day 7 (PND7). Since the release of ICH S6(R1) (2011), ePPND studies for biologics have replaced the former separate embryo-fetal and PPND study types. This work provides a retrospective analysis of pregnancy outcomes from 21 ePPND studies and group sizes of 14–24 animals per group. All studies reached the goal of at least six to eight infants on PND7, with overall losses ranging between 5 % and 45 %. Consistently, a group size of 14–24 maternal animals yielded more than six to eight infants on PND7. Therefore, it is suggested to reduce ePPND study group sizes from 20 to 14, yielding an animal number reduction of approx. 30 %.

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“…Because humans are commonly naïve to KLH epitopes prior to immunization (albeit with cross‐reactive responses to structurally similar endogenous or exogenous carbohydrate epitopes in some cases 14,15 ), KLH has advantages over alternate natural or therapeutically used antigens commonly used for HIC (e.g., varicella zoster or BaCG) which do not allow control of the degree, duration, and time‐elapsed since primary exposure. KLH has been used for over 50 years for TDAR/DTH assessment in both HIC and preclinical contexts 16–19 . Longstanding use has affirmed its utility as a safe and reliable model inducer of a TDAR/DTH response.…”

Section: Introductionmentioning

confidence: 99%

In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review

Drennan

Karponis

Richards

et al. 2022

Clinical Translational Sci

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An inter-laboratory retrospective analysis of immunotoxicological endpoints in non-human primates: T-cell-dependent antibody responses

Cited by 26 publications

References 4 publications

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (<i>Macaca fascicularis</i>)

In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review

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An inter-laboratory retrospective analysis of immunotoxicological endpoints in non-human primates: T-cell-dependent antibody responses

Cited by 26 publications

References 4 publications

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Inhibition of CRAC with a human anti-ORAI1 monoclonal antibody inhibits T-cell-derived cytokine production but fails to inhibit a T-cell-dependent antibody response in the cynomolgus monkey

Group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (&lt;i&gt;Macaca fascicularis&lt;/i&gt;)

In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review

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Group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (<i>Macaca fascicularis</i>)