A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials

Zsófia Pénzváltó, Jane Qian Chen, Clifford G Tepper, Ryan R. Davis, Matthew T. Silvestrini, Maxine Umeh-Garcia, Colleen A Sweeney, Alexander D Borowsky

Research output: Contribution to journalArticle

Abstract

In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDL UCD ”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDL UCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDL UCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDL UCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1 fvb2 and FVB/NTg(MMTV-PyVT Y315F/Y322F ) derived DB-7 fvb2 cell lines. The NDL UCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.

Original languageEnglish (US)
JournalJournal of Mammary Gland Biology and Neoplasia
DOIs
StatePublished - Jan 1 2019

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Immunotherapy
Breast Neoplasms
Cell Line
Transplants
Immunophenotyping
Neoplasms
Histology
Cell Culture Techniques
Transplantation
Phenotype
Gene Expression
Growth
In Vitro Techniques
Therapeutics

Keywords

  • Breast cancer
  • Erbb2
  • Immunotherapy
  • Mouse model
  • PD-L1
  • Syngeneic

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. / Pénzváltó, Zsófia; Chen, Jane Qian; Tepper, Clifford G; Davis, Ryan R.; Silvestrini, Matthew T.; Umeh-Garcia, Maxine; Sweeney, Colleen A; Borowsky, Alexander D.

In: Journal of Mammary Gland Biology and Neoplasia, 01.01.2019.

Research output: Contribution to journalArticle

Pénzváltó, Zsófia ; Chen, Jane Qian ; Tepper, Clifford G ; Davis, Ryan R. ; Silvestrini, Matthew T. ; Umeh-Garcia, Maxine ; Sweeney, Colleen A ; Borowsky, Alexander D. / A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. In: Journal of Mammary Gland Biology and Neoplasia. 2019.
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abstract = "In order to develop a practical model of breast cancer, with in vitro and syngeneic, immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDL UCD ”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDL UCD tumors in FVB/N mice exhibit high expression of ErbB2 and ErbB3 and signaling molecules downstream of ErbB2. The syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, detected and characterized using histology, immunophenotyping, and gene expression. NDL UCD cells also express PD-L1 in vivo and in vitro, and in vivo transplants are reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. This new NDL UCD cell line model is a practical alternative to the more commonly used 4T1 cells, and our previously described FVB/N-Tg(MMTV-PyVT)634Mul derived Met-1 fvb2 and FVB/NTg(MMTV-PyVT Y315F/Y322F ) derived DB-7 fvb2 cell lines. The NDL UCD cells have, so far, remained genetically and phenotypically stable over many generations, with consistent and reproducible results in immune intact preclinical cohorts.",
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