Inventors:
Jacqueline Parker - Birmingham AL, US
Richard Whitley - Birmingham AL, US
James Markert - Birmingham AL, US
International Classification:
A61K 39/245, C12N 7/01, A61P 35/00
Abstract:
A conditionally replicating, aneurovirulent recombinant herpes simplex virus is provided that includes a nucleic acid encoding an expressible chemokine. An expression control element is operably linked to the nucleic acid. A therapeutic composition includes a first conditionally replicating, aneurovirulent recombinant herpes simplex virus having a first nucleic acid encoding a first expressible cytokine operatively linked to an expression control element. A second such herpes simplex virus encoding a second expressible cytokine is also provided with a pharmaceutically acceptable carrier. Preferably, the second cytokine is a chemokine. In a particular embodiment, the first expressible cytokine increases availability of an immunoresponsive cell for activation. The activatable cell is CD4+, CD8+, NK, a dendritic cell, or a combination thereof. A second conditionally replicating, aneurovirulent, recombinant herpes simplex virus expresses a second cytokine in the same host cell as the first virus or alternatively, upon expression in a second host cell, resulting in the activation of the immunoresponsive cell. A method of tumor cell growth inhibition is provided that includes introduction of a therapeutically effective amount of an aforementioned therapeutic composition into a tumor of an individual such that two different cytokines are produced within the tumor to enhance the immune response in the individual that inhibits tumor cell growth. The first and second recombinant herpes simplex viruses are administered simultaneously, sequentially. Sequential administration is separated by a time period ranging from a few second to several days.