Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors

Herpes simplex virus amplicon vectors expressing RANTES (HSVrantes) and the T-cell costimulatory ligand B7.1 (HSVB7.1) were studied for their ability to elicit a tumor-specific T-cell response in a murine lymphoma model. HSVB 7.1- and HSVrantes-transduced EL4 cells expressed high levels of B7.1 and R ANTES as analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. Inoculation of ex vivo HSVB7.1 transduced cells in syngeneic mice resulted in regression of both transduced cells and nontransduced cell s inoculated contralaterally. Direct intratumoral injection of HSVB7.1 and/ or HSVrantes alone or in combination into established EL4 tumors led to com plete tumor regression in injected tumors as well as in nontransduced contr alaterally implanted tumor, whereas control tumors OF tumors injected with HSVlac expressing beta-galactosidase did not regress. Maximal protection wa s achieved with combined injection of HSVB7.1, and HSVrantes: mice showing tumor regression were resistant to rechallenge with parental EL4 cells, and tumor cell-specific cytolytic T-cell activity was observed in mice demonst rating regression. HSV amplicon-mediated delivery of immune effector molecu les may represent a useful strategy for immunotherapy in the setting of pre -existing tumor. (C) 1999 by The American Society of Hematology.