Use of herpes vectors for tumor therapy

Details Use of herpes vectors for tumor therapy Use of herpes vectors for tumor therapy

A - Human Necessities

61

K

A61K 35/76 (2006.01) A61K 38/19 (2006.01) A61K 38/20 (2006.01) A61K 48/00 (2006.01) C12N 7/01 (2006.01)

Patent

CA 2301327

Eliciting a systemic antitumor immune response, in a patient who presents with or who is at risk of developing multiple metastatic tumors of a given cell type, entails, in one embodiment, inoculating a tumor in the patient with a pharmaceutical composition consisting essentially of (A) a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells and (B) a pharmaceutically acceptable vehicle for the virus, such that an immune response is induced that is specific for the tumor cell type and that kills cells of the inoculated tumor and of a non-inoculated tumor. In another embodiment, the pharmaceutical composition also comprises a defective HSV vector which contains an expressible nucleotide sequence encoding at least one immune modulator. In another embodiment, the pharmaceutical composition contains a second HSV that infects tumor cells but that does not spread in normal cells. According to the latter approach, both the first HSV and the second HSV may have genomes that comprise, respectively, an expressible nucleotide sequence coding for at least one immune modulator. In another embodiment, the pharmaceutical composition comprises, in addition to a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells, a viral vector comprising at least one expressible nucleotide sequence coding for at least one immune modulator.

L'invention concerne des méthodes permettant de solliciter une réponse immunitaire anti-tumorale systémique chez un patient présentant ou risquant de développer des métastases multiples d'un type cellulaire donné. Un des modes d'application consiste à inoculer la tumeur du patient avec une composition pharmaceutique comprenant essentiellement (A) un virus herpès simplex (HSV) qui infecte les cellules tumorales mais ne se propage pas aux cellules normales et (B) un véhicule pharmaceutiquement acceptable pour le virus, afin d'induire une réponse immunitaire qui est spécifique au type cellulaire de la tumeur et qui provoque la destruction les cellules de la tumeur (Rt) et d'une tumeur non-inoculée (Lt). Dans un autre mode de réalisation la composition pharmaceutique comprend en outre un vecteur HSV défectueux qui contient une séquence nucléotidique pouvant être exprimée, codant au moins un immunomodulateur. Dans un autre mode de réalisation, la composition pharmaceutique contient un second HSV qui infecte les cellules tumorales mais ne se propage pas aux cellules normales. Dans cette dernière approche, le premier HSV et le second HSV peuvent comprendre des génomes qui comprennent respectivement une séquence nucléotidique exprimable codant au moins pour un immunomodulateur. Dans un autre mode de réalisation, la composition phamaceutique comprend, outre le virus herpès simplex (HSV) qui infecte les cellules tumorale mais ne se propage pas aux cellules normales, un vecteur viral comprenant au moins un séquence nucléotidique pouvant être exprimée, codant pour au moins un immunomodulateur.

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