Abstract
Background
DISC‐hGMCSF is a gH‐deleted HSV‐2 based vector expressing human GM‐CSF that has entered clinical trials for the therapy of metastatic melanoma. To determine whether this product also has potential to treat breast carcinoma, a series of in vitro and in vivo studies were made.
Methods
Breast carcinoma cell lines and primary cultures of breast carcinoma cells were infected with DISC‐GFP or DISC‐human‐GMCSF (DISC‐hGMCSF) and the number of GFP‐positive cells and GM‐CSF yields were determined. In vivo efficacy of DISC‐murine‐GMCSF (DISC‐mGMCSF) in combination with systemic chemotherapy was assessed in the murine 4T1 breast carcinoma model by direct injection into subcutaneous tumours.
Results
DISC‐hGMCSF was able to infect all breast carcinoma cell lines and the majority of primary breast carcinoma cultures with high efficiency, although culture‐to‐culture variability in infectability was noted in the latter. In the MCF‐7 breast carcinoma cell line, expression of hGMCSF was found to peak over the first 24 h post‐infection and drop to background levels by 7 to 14 days. In the 4T1 murine breast tumour model, injection of subcutaneous tumours led to a delay in tumour growth and, in rare cases, complete regression of visible tumour. DISC‐mGMCSF and DISC‐LacZ showed similar levels of efficacy. When mice were given simultaneous 5FU chemotherapy the effectiveness of DISC‐mGMCSF treatment was undiminished, and up to three out of ten mice showed complete absence of visible tumour.
Conclusions
DISC‐hGMCSF is able to infect human breast carcinoma cells at high efficiency and express GM‐CSF. DISC‐mGMCSF demonstrated efficacy in the murine 4T1 model, even during concomitant chemotherapy. Taken together these results indicate that DISC‐hGMCSF may have potential for the treatment of breast carcinoma. Copyright © 2003 John Wiley & Sons, Ltd.