Abstract 2401: IGF-IR peptide vaccine inhibits tumor growth via IFN-g-dependent biologic remodeling of the tumor

Abstract

Abstract The insulin-like growth factor (IGF) pathway plays an important role in breast cancer growth and metastasis. The majority of breast tumors overexpress the IGF-I receptor (IGF-IR). Increased IGF-IR signaling in breast cancer is correlated with a poor prognosis and is associated with disease that is resistant to chemotherapy, radiotherapy, and biologic therapy. Thus, therapeutically targeting the IGF-IR signaling pathway is a promising approach to treat breast cancer. We have determined that the IGF-IR is immunogenic in breast cancer. Furthermore, vaccination with MHCII IGF-IR-specific peptides p384-398, p575-589, p951-965, and p1122-1136 induces a CD4+ T cell-dependent anti-tumor immune response in Neu-transgenic mice. Preliminary data suggests that IGF-IR specific immunization results in both decreased proliferation and increased apoptosis of tumor cells. Antigen specific CD4+ T cells secrete IFN-g and we have demonstrated that the inhibition of tumor growth with the IGF-IR vaccine is dependent on IFN-g. We questioned the mechanism whereby IFN-g-secreting CD4+ T cells targeting IGF-IR could inhibit tumor growth. Studies suggest that tumor-associated IGF-IR activation is decreased in tumors from vaccinated mice, with concomitant upregulation in SOCS-3, which has been shown to be modulated by IFN-g. In addition, IFN-g stimulation of the tumor cell line derived from the Neu-transgenic mouse decreased IGF-IR activation and induced SOCS-3 expression. Thus, active immunization targeting IGF-IR may induce both immunologic and biologic effects resulting in inhibition of breast cancer growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2401.