Improving anti-cancer therapy by stromal remodelling
Worldwide Cancer Research
University of Western Australia
Despite recent breakthroughs, cancer immunotherapy remains challenging. One of the problems is that anti-tumour T cells - even when activated - do not reach the cancer core in sufficient numbers to be effective. The lead investigator’s laboratory has pioneered the field of tumour blood vessel normalization which significantly enhances T cell penetration into solid tumours, with proven anti-cancer effects. For clinical translation, mechanistic insights into these complex processes are urgently required. In this project, substantial preliminary data demonstrate an innovative and new approach to remodel the vascular bed, restore vessel integrity, improve tumour perfusion and enable massive lymphocyte influx into tumours. We will use mouse models of melanoma, including patient-derived melanoma xenografts in immune ‘humanized’ mice, to provide new insights into stromal remodelling and immune cell trafficking. Importantly, mechanistic insights will enable re-positioning of established drugs/small molecule inhibitors to specifically improve vessel function. Furthermore, we will evaluate drugs in the context of durable intratumoral effects, low toxicity and enhanced efficacy in immune combination therapies.
5.1 Pharmaceuticals