Comparison of Spontaneous Minor Lesions in Wild-caught and Laboratory-bred Monkeys.

Shimoi, Akihito; Kakinuma, Chihaya; Kuwayama, Chitose; Watanabe, Mitsutoshi

doi:10.1293/tox.11.85

Cited by 11 publications

(14 citation statements)

References 3 publications

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“…There are very few reports of this kind in the literature (Drevon-Gaillot et al 2006;Ito et al 1992;Lowenstine 2003;Shimoi et al 1998). Most other published reports are based on studies in zoo or wild-caught primates or in older animals (Bennett et al 1998;Scott 1999), which predictably have a spectrum of pathological findings that is slightly different from that of laboratory-raised animals used in toxicological studies.…”

Section: Discussionmentioning

confidence: 99%

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

et al. 2010

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The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in control cynomolgus monkeys. Data were collected from 570 monkeys (285 animals per sex), aged twelve to thirty-six months, from sixty regulatory studies evaluated at our laboratory between 2003 and 2009. The most common finding overall was lymphoplasmacytic infiltrates observed in the following incidence: liver (60.7%), kidneys (28.8%), heart (25.8%), salivary glands (21.2%), and stomach (12.1%). Inflammation also commonly occurred in the heart, kidneys, lungs, and stomach. The most common degenerative changes were localized fatty change in the liver, myocardial degeneration, and mineralization and pigment deposits in various tissues. Parathyroid, thyroid, and pituitary cysts; ectopic thymus in the parathyroid or thyroid gland; accessory spleen within the pancreas; and adrenohepatic fusion were among the most common congenital findings. Some incidental findings bearing similarities to drug-induced lesions were also encountered in various organs. It is hoped that the results presented here and elsewhere could form the groundwork for the creation of a reliable database of incidental pathology findings in laboratory nonhuman primates.

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Section: Discussionmentioning

confidence: 99%

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

et al. 2010

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“…A review of background findings in cynomolgus monkeys ( Macaca fascicularis ) from three different geographical origins published in 2006 5 , states that subacute gastritis is observed in 65 out of 90 cynomolgus monkeys and is characterized by a diffuse lymphoplasmacytic infiltration of the lamina propria of the stomach. Shimoi and co-workers (1998) 8 noted the presence of gastritis in laboratory-bred cynomolgus monkeys accompanied by atrophy of epithelial cells, but without the presence of ulceration and haemorrhage. Finally, Ito and co-workers (1996) 7 noted the presence of mononuclear cells and dilatation of gastric glands in cynomolgus monkeys in a study in 1996.…”

Section: Discussionmentioning

confidence: 99%

“…Ito and co-workers (1992) 7 described mononuclear cell infiltration into the stomachs of 81 out of 221 male cynomolgus monkeys and 44 out of 221 female cynomolgus monkeys. Shimoi and co-workers (1998) 8 noted the presence of gastritis in laboratory-bred cynomolgus monkeys accompanied by atrophy of epithelial cells, but without the presence of ulceration and haemorrhage. Mucosal atrophy, inflammatory cell infiltration and dilatation of gastric glands were noted in the stomachs of a small number of marmosets in a study in 1996 9 .…”

Section: Introductionmentioning

confidence: 99%

The Incidence of Lymphoplasmacytic Gastritis in the Fundus and Antrum of Cynomolgus Monkey (<i>Macaca fascicularis</i>) Stomachs

McKeag

McInnes

2012

J Toxicol Pathol

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Lymphoplasmacytic gastritis is a concern for toxicological pathologists reading preclinical, non-human primate toxicity studies because subtle gastric changes which could be treatment-related may be masked and gastritis lesions may be confused with treatment-related effects and thus a gastric finding may be incorrectly assigned as a treatment-related lesion. This paper discusses the incidence of lymphoplasmacytic gastritis in cynomolgus monkeys at a contract research organization. The incidence of lymphoplasmacytic gastritis in the fundus and antrum of control cynomolgus monkeys on 18 non-gastric compound studies, was scored. The average fundus score ranged from 0.3 to 1.5 and the average antral score ranged from 0.9 to 3.5 in the cynomolgus monkey stomachs examined. The number of affected control animals in a study ranged from 0 to 5 control animals. No correlation between the route of vehicle administration and the severity or incidence of the lesions was noted. The percentage incidence of affected animals ranged from 0 to 100%. An increased incidence lymphoplasmatic gastritis from 2000 to 2004 was noted. The implications of lymphoplasmacytic gastritis in cynomolgus monkeys used for acute toxicity studies are discussed.

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“…The assessment of potential pathological changes in macaque tissues showed no macroscopic changes in the heart, brain, lung, kidney, liver, spleen, spinal cord, skin and bone marrow. Moreover, there were no microscopic changes related to the CAR T‐cell infusion (Supplementary table 1), although the infiltration of cynomolgus mononuclear cells was detected in the liver and kidney, which is normally observed in cynomolgus macaques 21,22 …”

Section: Resultsmentioning

confidence: 97%

“…Moreover, there were no microscopic changes related to the CAR T-cell infusion (Supplementary table 1), although the infiltration of cynomolgus mononuclear cells was detected in the liver and kidney, which is normally observed in cynomolgus macaques. 21,22…”

Section: No Pathological Changes Were Observed In the Recipients Of Cmentioning

confidence: 99%

Autologous non‐human primate model for safety assessment of piggyBac transposon‐mediated chimeric antigen receptor T cells on granulocyte–macrophage colony‐stimulating factor receptor

et al. 2020

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Objectives Chimeric antigen receptor (CAR)‐T cell therapy redirected to specific antigens on tumor cells is a promising immunotherapy strategy for various cancers. Most target antigens are also expressed on normal tissues at varying levels, and therefore, a considerable challenge in the field is determining safety profiles, including life‐threatening off‐tumor and off‐target toxicities. The granulocyte–macrophage colony‐stimulating factor receptor (hGMR) is a promising target for CAR T‐cell therapy for a subset of acute myelocytic leukaemia, although it is also expressed on normal cells including monocytes, macrophages, CD34‐positive haematopoietic cells and vascular endothelial cells. hGMR and other immune‐related proteins are highly conserved between humans and cynomolgus macaques (Macaca fascicularis). Therefore, in this study, we engineered cynomolgus T cells to express CAR molecules redirected to hGMR by piggyBac (PB) transposon‐based gene transfer and adoptively transferred autologous hGMR‐CAR T cells into cynomolgus macaques. Methods We established PB‐mediated human GMR (hGMR)‐specific CAR T cells using cynomolgus peripheral blood mononuclear cells and transferred them into autologous individuals, and evaluated the potential toxicity related to hGMR‐CAR T cells. Results hGMR‐CAR T cells did not exert overt organ toxicities such as bone marrow suppression, monocytopenia and vasculitis, although they recognised and killed cynomolgus monocytes and macrophages in vitro. Conclusion Although our model did not simulate a tumor‐bearing model, it supports the safety of hGMR‐CAR T cells and demonstrates the usefulness of a non‐human primate model to evaluate the safety of T‐cell products by assessing off‐tumor/off‐target toxicity before clinical trials.

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Comparison of Spontaneous Minor Lesions in Wild-caught and Laboratory-bred Monkeys.

Cited by 11 publications

References 3 publications

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

Incidences and Range of Spontaneous Findings in Control Cynomolgus Monkeys (Macaca fascicularis) Used in Toxicity Studies

The Incidence of Lymphoplasmacytic Gastritis in the Fundus and Antrum of Cynomolgus Monkey (<i>Macaca fascicularis</i>) Stomachs

Autologous non‐human primate model for safety assessment of piggyBac transposon‐mediated chimeric antigen receptor T cells on granulocyte–macrophage colony‐stimulating factor receptor

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