Overcoming immune suppression in cancer patients is a major challenge for the success of cancer immunotherapy. TGF-beta and its receptors are expressed in essentially all tissues, and they have been found to be important in many cellular processes including cell growth inhibition. The inhibition of TGF-beta signaling has been shown to have an inhibitory effect on tumor growth. However, TGF-beta also has immunosuppressive properties.
Cancer vaccines are one of many therapies available for treatment and prevention. In particular, vaccines that elicit immune responses have been used to treat or control tumor growth that has evaded immunosurveillance. However, these vaccines have demonstrated limited success.
Available for licensing is a method for synergistically affecting tumor growth involving the administration 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 may 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. The administration of the 1D11.16 anti-TGF-beta antibody in combination with the human papilloma virus E7(49-57) peptide enhances tumor regression in an animal model. The administration of the 1D11.16 anti-TGF-beta antibody in combination with irradiated CT26 cells enhances tumor regression in another mouse model. The investigators found that administering the combination of agents is more effective than the sum of their individual effects.
A method of cancer combination therapy based on immunotherapeutics.
M Terabe et al. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med. 2003 Dec 1;198(11):1741-1752. [PubMed abs]
• U.S. Provisional Application No. 60/654,329 filed 17 Feb 2005 (HHS Reference No. E-019-2005/0-US-01)
• PCT Application No. PCT/US2006/005888 filed 16 Feb 2006, which published as WO 2006/089251 on 24 Aug 2006 (HHS Reference No. E-019-2005/0-PCT-02)
• U.S. Patent Application No. 11/816,410 filed 15 Aug 2007 (HHS Reference No. E-019-2005/0-US-06)
Masaki Terabe (NCI) et al.
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