Development of an ErbB‐overexpressing A‐431 Optical Reporting Tumor Xenograft Model to Assess Targeted Photodynamic Therapy Regimens

AbstractTo better assess the efficacy of erbB‐targeted therapies, it would help to have optical reporting human tumor xenograft models that abundantly express erbB receptors. A‐431 cells have frequently been used in erbB1‐targeting studies, but a well‐characterized optical reporting version of the cell line has not been readily available. In this study, optical reporting A‐431 clones were developed that express both a fluorescent protein reporter (green, GFP; or red, RFP) and a bioluminescent reporter, firefly luciferase. Reporter genes were transduced into cells using commercial lentiviral vectors, and clonal selection was carried out using a series of procedures. A number of clones were isolated for further characterization. A GFP/luciferase clone, A‐431/D4, and an RFP/luciferase clone, A‐431/G4, were obtained that exhibit erbB1 expression levels and tumor growth kinetics similar to the parental cells. To demonstrate the utility of the optical reporting clones, A‐431/G4 tumors were grown subcutaneously in nude mice and treated with vascular‐targeted photodynamic therapy (PDT), which targets the angiogenic consequences of erbB signaling. The A‐431/G4 tumor model permitted highly sensitive longitudinal monitoring of PDT treatment response using optical imaging. A‐431/D4 and A‐431/G4 optical reporting tumor models should also prove useful for assessing therapies that directly target the erbB1 receptor.