SUICIDE GENE-THERAPY FOR PLASMA-CELL TUMORS

Suicide gene therapy for plasma cell tumors was attempted in severe co mbined immunodeficient (SCID) mice injected with human myeloma cell li nes, initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcuteanously (SC) int o SCID mice could be eradicated by the administration of ganciclovir ( GCV). Furthermore, an in vivo bystander effect was noticed when mice r eceived mixtures of HSVtk-positive and nontransduced cells, Unexpected ly, a ''distant by-stander'' effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller an d had increased frequency of apoptotic figures and decreased mitotic f requency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice. (C) 1996 by The Americ an Society of Hematology.