Abstract 2444: The integrin alpha10beta1 antibody TARG10 reduces tumor growth and metastasis of triple negative breast cancer

Cancer Research(2022)

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摘要
Abstract Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that accounts for 10-15% of all breast cancer diagnoses. It is far more aggressive than other breast cancer types due to a higher degree of metastases and frequent relapses following current treatment options. Integrin alpha10beta1 is a collagen binding receptor that has emerged as a promising new cancer target due to its role in tumor cell proliferation and migration. The aim of the present study was to investigate the function blocking activity of the human integrin alpha10beta1 antibody TARG10 on growth and metastasis of TNBC.We have found that integrin alpha10beta1 is highly expressed in TNBC, with minimal expression in healthy tissue, and that high expression is correlated with poor prognosis in TNBC patients. In vitro studies showed significant inhibiting effects of TARG10 on the adhesion, migration, proliferation, and viability of TNBC cells. In an orthotopic xenograft TNBC model, TARG10 confirmed inhibitory effects on both tumor growth and metastasis as demonstrated by In Vivo Imaging System (IVIS-CT). The effect on metastasis was further demonstrated in a tail vein xenograft TNBC model of experimental metastasis. Pharmaceutical evaluation demonstrated excellent developability properties, including low post translational liabilities, high melting point, low aggregation and high yield.In summary, integrin alpha10beta1 represents a promising target for directed antibody-based therapy of TNBC. Our in vitro and in vivo data supports pre-clinical and clinical development of TARG10 as a candidate drug for treatment of patients with triple negative breast cancer. Citation Format: Katarzyna Masoumi, Xiaoli Huang, Anna Mirkov, Kristine Smedenfors, Per Norlén, Evy Lundgren-Åkerlund. The integrin alpha10beta1 antibody TARG10 reduces tumor growth and metastasis of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2444.
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integrin alpha10beta1 antibody,breast cancer,tumor growth,metastasis
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