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Blood, Vol. 93 No. 2 (January 15), 1999:
pp. 643-654
Eradication of Pre-Established Lymphoma Using Herpes Simplex
Virus Amplicon Vectors
Mahmood Kutubuddin,
Howard J. Federoff,
Pia M. Challita-Eid,
Marc Halterman,
Brian Day,
Meredith Atkinson,
Vicente Planelles, and
Joseph D. Rosenblatt
From the Department of Microbiology and Immunology, the Division of
Molecular Medicine and Gene Therapy, Department of Neurology,
University of Rochester Cancer Center, Department of Medicine,
University of Rochester, Rochester, NY.
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. HSVB7.1- and HSVrantes-transduced EL4 cells expressed
high levels of B7.1 and RANTES 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 cells
inoculated contralaterally. Direct intratumoral injection of HSVB7.1
and/or HSVrantes alone or in combination into established EL4
tumors led to complete tumor regression in injected tumors as well as
in nontransduced contralaterally implanted tumor, whereas control
tumors or tumors injected with HSVlac expressing  -galactosidase did
not regress. Maximal protection was 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 demonstrating regression. HSV
amplicon-mediated delivery of immune effector molecules may represent a
useful strategy for immunotherapy in the setting of pre-existing tumor.
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