Abstract 96: A novel in vivo preclinical model for the study of human tumor angiogenesis with human vessels

Abstract

Abstract The preclinical assessment of anti-angiogenic drug efficacy is hampered by the lack of availability of suitable model systems to study anti-human therapies. Good in vitro assays exist for testing anti-human-specific therapies but these are let down by the lack of robust translatable in vivo models. Currently available preclinical models such as the matrigel plug assay and the window chamber assay focus on the angiogenesis of mouse vessels which may not be truly reflective of the influence of test items on human vasculature, and in vivo models to study the angiogenesis of human tumors by human vessels are unfortunately lacking. We have developed a sophisticated model to address this using adult human skin engrafted onto immunocompromised CB17-SCID mice. Angiogenesis of the skin follows, with human and host vessels anastomosing, resulting in a viable skin graft containing functioning human CD31-labelled vessels. This skin graft can be intradermally injected with a cell line of interest, such as the human melanoma cell line A375, and the ensuing tumors contain human vessels as evidenced by immunohistochemistry with a human-specific anti-CD31 antibody. Using the Aperio® Scanscope and FDA-approved microvessel analysis algorithm, 5-10 human vessels per mm2 of human tumor are observed. Furthermore, the model has the potential to be used in combination with non-invasive in vivo imaging techniques to assess tumor growth inhibition in response to therapies in a longitudinal fashion. This novel technique could potentially enable the rapid preclinical testing of anti-angiogenic anti-human therapies to help provide a go/no-go decision prior to costly clinical trials. Citation Format: Kirsty A. Holden, Michael A. Batey, Martyn Bottomley, Catherine Booth. A novel in vivo preclinical model for the study of human tumor angiogenesis with human vessels. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 96. doi:10.1158/1538-7445.AM2014-96