The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies

Fallon K. Noto, Jaya Sangodkar, Bisoye Towobola Adedeji, Sam Moody, Christopher B. McClain, Ming Tong, Eric Ostertag, Jack Crawford, Xiaohua Gao, Lauren Hurst, Caitlin M. O'Connor, Erika N. HansonID, Sudeh Izadmehr, Rita Tohme, Jyothsna Narla, Kristin LeSueur, Kajari Bhattacharya, Amit Rupani, Marwan K. Tayeh, Jeffrey W. InnisMatthew D. Galsky, B. Mark Evers, Analisa DiFeo, Goutham Narla, Tseten Y. Jamling

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We have created the immunodeficient SRG rat, a Sprague-Dawley Rag2/Il2rg double knockout that lacks mature B cells, T cells, and circulating NK cells. This model has been tested and validated for use in oncology (SRG OncoRat®). The SRG rat demonstrates efficient tumor take rates and growth kinetics with different human cancer cell lines and PDXs. Although multiple immunodeficient rodent strains are available, some important human cancer cell lines exhibit poor tumor growth and high variability in those models. The VCaP prostate cancer model is one such cell line that engrafts unreliably and grows irregularly in existing models but displays over 90% engraftment rate in the SRG rat with uniform growth kinetics. Since rats can support much larger tumors than mice, the SRG rat is an attractive host for PDX establishment. Surgically resected NSCLC tissue from nine patients were implanted in SRG rats, seven of which engrafted and grew for an overall success rate of 78%. These developed into a large tumor volume, over 20,000 mm3 in the first passage, which would provide an ample source of tissue for characterization and/or subsequent passage into NSG mice for drug efficacy studies. Molecular characterization and histological analyses were performed for three PDX lines and showed high concordance between passages 1, 2 and 3 (P1, P2, P3), and the original patient sample. Our data suggest the SRG OncoRat is a valuable tool for establishing PDX banks and thus serves as an alternative to current PDX mouse models hindered by low engraftment rates, slow tumor growth kinetics, and multiple passages to develop adequate tissue banks.

Original languageEnglish
Article numbere0240169
JournalPLoS ONE
Volume15
Issue number10
DOIs
StatePublished - Oct 2020

Bibliographical note

Publisher Copyright:
© 2020 Noto et al.

ASJC Scopus subject areas

  • General

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