Biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation

Autologous hematopoietic stem cell transplantation after myelosuppressive c hemotherapy is used for the treatment of high-risk breast cancer and other solid tumors. However, contamination of the autologous graft with tumor cel ls may adversely affect outcomes. Human hematopoietic bone marrow cells are resistant to herpes simplex virus type 1 (HSV-1) replication, whereas huma n breast cancer cells are sensitive to HSV-1 cytotoxicity. Therefore, we ex amined the utility of G207, a safe replication-competent multimutated HSV-1 vector, as a biological purging agent for breast cancer in the setting of stem cell transplantation. G207 infection of human bone marrow cells had no effect on the proportion or clonogenic capacity of CD34(+) cells but did e nhance the proliferation of bone marrow cells in culture and the proportion of CD14(+) and CD38(+) cells. On the other hand, G207 at a multiplicity of infection of 0.1 was able to purge bone marrow of contaminating human brea st cancer cells. Because G207 also stimulates the proliferation of human he matopoietic cells, it overcomes a limitation of other purging methods that result in delayed reconstitution of hematopoiesis. The efficient infection of human bone marrow cells in the absence of detected toxicity suggests tha t HSV vectors may also prove useful for gene therapy to hematopoietic proge nitor cells.