Human ERBB2 Stable Cell Line - MC38

Existing mouse models of HER2+ cancer are based on overexpression of the rodent Neu/Erbb2 homologous gene, but these are incompatible with human HER2 (huHER2)-targeted therapeutics. Researchers have established a human HER2+ mouse model by generating the ERBB2 stable cell line MC38 to better study immune mechanisms. Unlike the use of immunodeficient xenografts or transgenic models, this model allows for the assessment of natural anti-tumor immune responses. By expressing a truncated form of human HER2, HER2T, in the mouse colorectal cancer MC38 cell line, the researchers constructed this model. After validation, they treated with lysogenic blistering stomatitis virus (VSVΔ51) and the clinically approved antibody-drug coupling T-DM1 and assessed tumor control, survival, and immune response. The results showed that the combination of VSVΔ51 and T-DM1 had a significant curative effect and triggered extensive immune memory. Further immunoassays demonstrated CD4+ T-cell infiltration in tumors, activation of B cells, NK cells, and dendritic cells, and tumor-reactive serum IgG. This study demonstrated that the ERBB2 stable cell line MC38 was able to efficiently assess the efficacy of human HER2-targeted therapies in an immunologically sound in vivo setting.

Figure 1. To confirm HER2T expression in the tumors, the researchers implanted 4T1.2 and 4T1.2-HER2T tumors subcutaneously or in situ into BALB/c mice, respectively. The tumors were extracted after 25 days, and after dissociation, the HER2T levels were quantified by flow cytometry or qRT-PCR, which demonstrated that the cell-surface HER2T and HER2T mRNA expression remained stable. Homologous models of other cell lines transduced with HER2T also showed >80% tumor formation. These models included subcutaneous tumors of colon cancer in MC38 mice (4/5, 80%). (Taha Z, et al., 2023)