Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database

Begley, Dale A.; Sundberg, John P.; Krupke, Debra M.; Neuhauser, Steven B.; Bult, Carol J.; Eppig, Janan T.; Morse, Herbert C.; Ward, Jerrold M.

doi:10.1016/j.yexmp.2015.07.004

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…Two human cell lines, Raji and Hela, used as positive references resulted in significant tumor growth and consequent death of mice. Data on the incidence of spontaneous tumors are not available for immunodeficient mice but are available for other mouse strains (20,21). As expected, GvHD was observed in immunodeficient mice receiving anti-CD19 CAR-T cells.…”

Section: Discussionmentioning

confidence: 74%

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy

Hu¹,

Ko²,

Dai³

et al. 2020

Ann Transl Med

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Background: Autologous chimeric antigen receptor (CAR) T cell therapy is a promising therapeutic strategy for treating hematologic malignancies. A spectrum of serious complications caused by CAR-T cells has caught great attention. We developed a novel CAR against CD19 namely UWC19, consisting anti-CD19 single-chain variable fragment (scFv) hinged with 4-1BB and CD3z signaling domains. In this study, preclinical assessments of UWC19 were conducted to evaluate the safety and efficacy in vitro and in vivo. Methods: To evaluate the binding activity of UWC19 cells to CD19, we measured the saturation degree of CAR with human CD19 molecules using flow cytometry in vitro. The antitumor efficacy of UWC19 cells was determined by in vitro cytotoxicity assay against CD19 positive cells and in vivo using a xenograft mouse model. Cross tissue reactivity of UWC19 cells was examined by co-culturing with cell lines from difference human tissues. Tumorigenicity was determined by subcutaneously injecting UWC19 in immunodeficient mice. Persistence was analyzed using quantitative PCR. Results: We showed that UWC19 CAR T cells exerted highly specific binding affinity and cytotoxicity against CD19+ cells in vitro. In vivo, UWC19 CAR T cells are able to fully control disease progression in a Raji-xenografted immunodeficient mouse model. UWC19 exerted no obvious effects on the mean body mass and graft versus host disease were observed in surviving mice. We showed that UWC19 cells specifically recognized and eliminated CD19 positive cells, whereas CD19 negative cells were much less affected. No tumorigenicity of UWC19 in immunodeficient mice was observed. Conclusions: UWC19 treatment effectively eliminated CD19 positive tumor cells with favorable toxicity profile. The findings suggest encouraging clinical prospects for its use in patients with CD19 positive B cell malignancies. Our study presented an alternative evaluation strategy for CAR-T cell products.

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Section: Discussionmentioning

confidence: 74%

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy

Hu¹,

Ko²,

Dai³

et al. 2020

Ann Transl Med

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“…In humans, GBHs have been shown to increase the risk ratios for non-Hodgkins lymphomas (NHL) in several meta-analyses [2,[57][58][59]. For over 30 years, mouse models have been studied and evaluated as surrogates for NHL [60][61][62][63][64]. Classification systems for humans and mice indicate a strong similarity between malignant lymphomas in mice and NHL in humans.…”

Section: Related Findings From the Peer-reviewed Literaturementioning

confidence: 99%

A comprehensive analysis of the animal carcinogenicity data for glyphosate from chronic exposure rodent carcinogenicity studies

Portier

2020

Environ Health

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Since the introduction of glyphosate-tolerant genetically-modified plants, the global use of glyphosate has increased dramatically making it the most widely used pesticide on the planet. There is considerable controversy concerning the carcinogenicity of glyphosate with scientists and regulatory authorities involved in the review of glyphosate having markedly different opinions. One key aspect of these opinions is the degree to which glyphosate causes cancer in laboratory animals after lifetime exposure. In this review, twenty-one chronic exposure animal carcinogenicity studies of glyphosate are identified from regulatory documents and reviews; 13 studies are of sufficient quality and detail to be reanalyzed in this review using trend tests, historical control tests and pooled analyses. The analyses identify 37 significant tumor findings in these studies and demonstrate consistency across studies in the same sex/species/strain for many of these tumors. Considering analyses of the individual studies, the consistency of the data across studies, the pooled analyses, the historical control data, non-neoplastic lesions, mechanistic evidence and the associated scientific literature, the tumor increases seen in this review are categorized as to the strength of the evidence that glyphosate causes these cancers. The strongest evidence shows that glyphosate causes hemangiosarcomas, kidney tumors and malignant lymphomas in male CD-1 mice, hemangiomas and malignant lymphomas in female CD-1 mice, hemangiomas in female Swiss albino mice, kidney adenomas, liver adenomas, skin keratoacanthomas and skin basal cell tumors in male Sprague-Dawley rats, adrenal cortical carcinomas in female Sprague-Dawley rats and hepatocellular adenomas and skin keratocanthomas in male Wistar rats.

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“…Traditional textbooks continue to serve a useful purpose with detailed images of normal anatomy [43] as well as gross and histologic lesions seen in mutant mice [44,42]. In addition, there are specialized website databases, such as the Mouse Tumor Biology Database (http://tumor.informatics.jax.org/mtbwi/index.do) [45–48], which focuses on cancer models, or more generalized mouse pathology databases such as the European Mouse Pathology Consortium website (http://www.pathbase.net/), whereby one can also access the more specific skin pathology database, see http://skinbase.org [49–51]. …”

Section: Introductionmentioning

confidence: 99%

Skin Diseases in Laboratory Mice: Approaches to Drug Target Identification and Efficacy Screening

Sundberg

Silva

McPhee

et al. 2016

Methods in Molecular Biology

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A large variety of mouse models for human skin, hair, and nail diseases are readily available from investigators and vendors worldwide. Mouse skin is a simple organ to observe lesions and their response to therapy, but identifying and monitoring the progress of treatments of mouse skin diseases can still be challenging. This chapter provides an overview on how to use the laboratory mouse as a preclinical tool to evaluate efficacy of new compounds or test potential new uses for compounds approved for use for treating an unrelated disease. Basic approaches to handling mice, applying compounds, and quantifying effects of the treatment are presented.

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Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database

Cited by 6 publications

References 31 publications

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+ B cell malignancy

A comprehensive analysis of the animal carcinogenicity data for glyphosate from chronic exposure rodent carcinogenicity studies

Skin Diseases in Laboratory Mice: Approaches to Drug Target Identification and Efficacy Screening

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