Modification of a Popular Syngeneic Murine Mammary Tumor Model for Immunotherapy Studies

Abstract EN

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.