Synergistic effect of tgf-beta blockade and immunogenic...

A - Human Necessities – 61 – K

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A61K 39/395 (2006.01) A61K 39/00 (2006.01) A61K 39/12 (2006.01) A61K 41/00 (2006.01) A61P 35/00 (2006.01) A61P 35/02 (2006.01) A61P 35/04 (2006.01) A61P 37/04 (2006.01) C07K 14/025 (2006.01) C07K 16/22 (2006.01)

Patent

CA 2598090

Methods are provided herein for synergistically affecting tumor growth in a subject, involving the administration to the subject of an agent that blocks the TGF- .beta. signaling pathway in combination with an immunogenic agent. The agent that blocks the TGF-.beta. signaling pathway is believed to inhibit the immunosuppressive effects of TGF-.beta., while the immunogenic agent is believed to enhance an immune response. Surprisingly, the combination of such elements produces a synergistic effect. In one embodiment, the administration of the IDl 1.16 anti-TGF-.beta. antibody in combination with the human papilloma virus E7(49-57) peptide enhances tumor regression and tumor-specific CTL response in the subject. In another embodiment, the administration of the IDl 1.16 anti-TGF-.beta. antibody in combination with irradiated CT26 cells enhances tumor regression in the subject. The method of administering the combination of agents to the subject is more effective than the administration of each agent individually, or the sum of their individual effects.

L'invention concerne des procédés ayant un effet synergique sur la croissance tumorale chez un sujet, et qui comprennent l'administration combinée audit sujet d'un agent bloquant la voie de signalisation du TGF-ß et d'un agent immunogène. L'agent qui bloque la voie de signalisation du TGF-ß inhibe les effets immunosuppresseurs du TGF-ß, alors que l'agent immunogène accroît la réponse immunitaire. La combinaison de ces éléments produit étonnamment un effet synergique. Dans une forme de réalisation, l'administration combinée de l'anticorps anti-TGF-ß 1D11.16 et du peptide E7(49-57) du papillomavirus humain accroît la régression tumorale et la réaction spécifique de tumeur des lymphocytes T cytotoxiques chez le sujet. Dans une autre forme de réalisation, l'administration combinée de l'anticorps anti-TGF-ß 1D11.16 et de cellules CT26 irradiées accroît la régression tumorale chez le sujet. Le procédé d'administration au sujet des agents combinés est plus efficace que l'administration de chaque agent individuellement, ou plus efficace que la somme des effets individuels.

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