Abstract 3397: Intrinsic factors from patient's tumor help neovascularization in an ex vivo platform

Abstract

Abstract Neovascularization is considered as a major event during embryonic development, found to be deregulated in several pathological conditions including malignancies. Factors secreted by tumor cells trigger a cascade of events which in turn play a critical role in the initiation and sprouting of tumor-specific-sustained-vasculature subsequently led to dramatic expansion of primary tumors, invasion and metastasis. Increasing evidence suggested that modulation of tumor cell specific intrinsic mechanisms which are accountable for tumor vasculogenesis would have therapeutic benefits to the patients even at later stages of disease. Therefore screening of such potential anti-angiogenic agents necessitates engineering a system where tumor vasculogenic environment is well preserved at micro-architecture level close to that of patient's native settings. Such a platform developed by Mitra Biotech, CANScriptTM demonstrated a high level of correlation to clinical outcome for many chemotherapeutics as well as targeted drugs in multiple solid and hematological cancers. Our CANScriptTM platform was being effectively validated for the retention of vascular phenotypes along with their immune and stromal counterparts, and their associated signaling networks. When patient derived tumor specimens were cultured in a two chambers microplates with human umbilical vein endothelial cells’ (HUVECs) in the presence of autologous ligands and customized matrix support, the native mediators released from tumor cells instigated complete formation of mature sprouts within 24 hours compared to HUVEC cells alone. In this platform we also assessed the anti-tumor efficacy of a known anti-angiogenic agents. The response to VEGF inhibitor was in turn measured by functional parameters like tumor morphology, anti-proliferative and apoptotic effects in combination with anti-angiogenic activity for the human tumors enrolled in the study. Treatment with VEGF inhibitor alone resulted in the abrogation of angiogenic crosstalk and transmission of signals from tumor cells to vessels. In addition to capturing anti-tumor efficacy of drugs using this platform technology, we were also able to dissect and better understand intervening strategies targeting tumor angiogenesis and vasculogenesis mechanisms under ex vivo conditions recreating in vivo like milieu. Citation Format: Baraneedharan Ulaganathan, Allen Thayakumar B, Manoj Rajappa, Ayyappan Velu, Arun Prasath, Kamal Ameer, Nilesh Brijwani, Padhma Radhakrishnan, Biswanath Majumder, Pradip K. Majumder, Saravanan Thiyagarajan. Intrinsic factors from patient's tumor help neovascularization in an ex vivo platform. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3397.