Abstract
To facilitate the evaluation of immunotherapeutic intervention against malignant diseases, it is desirable to have a syngeneic tumor model that closely resembles the growth pattern of human tumors. Murine 4T1 breast cancer model is known for its metastatic properties that mimic its human counterpart. However, a drawback of this model is the lack of an identified tumor antigen to function as a therapeutic target for immunologic intervention. We used the piggyBac transposon system to stably transduce a tumor antigen, the human epidermal growth factor receptor 2 gene (HER2), into this tumor cell. In vitro characterization shows that the newly established cells have a similar growth pattern as the parental line. In vivo evaluation shows that host immune response was generated against the HER2 tumor antigen, despite the high homology between HER2 and its murine counterpart (neu gene). When implanted into immune-deficient mice, the HER2-expressing 4T1 cells readily formed sizable tumors, indicating that these cells are useful for evaluating the therapeutic effect of adoptively transferred cytotoxic T cells that are specifically raised or modified to target the HER2 tumor antigen.
Highlights
The benefit of preclinical tumor models for evaluating cancer therapeutics depends largely on whether the tumors growing in animals closely mimic the characteristics of the human counterpart
The most frequently used preclinical models are those from tumor cell implantation, as they are controlled as compared with chemically induced tumors or those developed from genetic alterations
Metastases of 4T1 tumor cells are efficient and usually occur within 2–4 weeks after tumor implantation; the 4T1 murine breast cancer model is a valid, useful tumor model and has been widely used in studies for evaluating antitumor effects of many cancer therapeutics [3], especially those designed for immunologic interventions [4, 5]
Summary
The benefit of preclinical tumor models for evaluating cancer therapeutics depends largely on whether the tumors growing in animals closely mimic the characteristics of the human counterpart. While xenografted tumors must be grown in immune deficient animals, syngeneic tumors are grown in animals whose immune systems are intact This is an especially desirable characteristic since the efficacy of many cancer therapeutics can only be truly evaluated in the presence of an intact host immune function. Metastases of 4T1 tumor cells are efficient and usually occur within 2–4 weeks after tumor implantation; the 4T1 murine breast cancer model is a valid, useful tumor model and has been widely used in studies for evaluating antitumor effects of many cancer therapeutics [3], especially those designed for immunologic interventions [4, 5]
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