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, Joseph D Rosenblatt

Research output: Contribution to journalArticle

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Abstract

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 β-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.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalBlood
Volume93
Issue number2
StatePublished - Jan 15 1999
Externally publishedYes

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Simplexvirus
Viruses
Tumors
Lymphoma
Chemokine CCL5
Neoplasms
T-cells
T-Lymphocytes
Galactosidases
Immunosorbents
Injections
Flow cytometry
Direct injection
Immunotherapy
Assays
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Cells
Ligands
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

Kutubuddin, M., Federoff, H. J., Challita-Eid, P. M., Halterman, M., Day, B., Atkinson, M., ... Rosenblatt, J. D. (1999). Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors. Blood, 93(2), 643-654.

Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors. / Kutubuddin, Mahmood; Federoff, Howard J.; Challita-Eid, Pia M.; Halterman, Marc; Day, Brian; Atkinson, Meredith; Planelles, Vicente; Rosenblatt, Joseph D.

In: Blood, Vol. 93, No. 2, 15.01.1999, p. 643-654.

Research output: Contribution to journalArticle

Kutubuddin, M, Federoff, HJ, Challita-Eid, PM, Halterman, M, Day, B, Atkinson, M, Planelles, V & Rosenblatt, JD 1999, 'Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors', Blood, vol. 93, no. 2, pp. 643-654.
Kutubuddin M, Federoff HJ, Challita-Eid PM, Halterman M, Day B, Atkinson M et al. Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors. Blood. 1999 Jan 15;93(2):643-654.
Kutubuddin, Mahmood ; Federoff, Howard J. ; Challita-Eid, Pia M. ; Halterman, Marc ; Day, Brian ; Atkinson, Meredith ; Planelles, Vicente ; Rosenblatt, Joseph D. / Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors. In: Blood. 1999 ; Vol. 93, No. 2. pp. 643-654.
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