A Technology Platform for Next Generation VNAR Based Oncology Medicines

点击翻译按钮获取中文摘要

"Despite marked improvements in outcomes for cancer patients, 35% will succumb to the disease. First line chemotherapy treatments generally rely on the sensitivity of fast-growing cancers being more susceptible to toxic agents than ""normal"" healthy cells. The unpleasant side-effects of this treatment, together with a poor prognosis means there is an urgent need for new targeted therapeutics to improve patient health. Developments to-date have included the targeted delivery of drugs to cancer cells as a way of limiting toxic side effects on healthy tissues. Targeted therapies based on monoclonal antibodies have been used with some success. However, their ""killing power"" can be ineffective against larger solid tumours.To ramp-up their potency, tumour targeting antibodies have been conjugated with highly potent cytotoxic drugs, and antibodies have been engineered that simultaneously target two different cancer proteins in order to improve tumour selectivity. Whilst these antibody drug conjugates (ADCs) and bi-specific antibody approaches show promise, the large size and complexity of antibodies limits their tumour penetrating ability and the ability to engineer therapeutic improvements. Furthermore, the cost of manufacture and off-target side effects are still significant problems for these agents. Consequently, next generation approaches using 'smaller' protein therapeutics with improved tumour penetration, increased stability and less toxicity hold great promise.To meet this challenge, the aim of this project is to build a platform technology for the accelerated development and optimisation of novel oncology medicines based on antibody-like single domain receptors found in sharks (VNARs).Shark VNAR domains are the smallest naturally occurring antigen binding domain in the animal kingdom and their properties are potentially advantageous for cancer therapy. In an initial collaboration between Almac Discovery and Elasmogen, we have shown that high affinity VNARs can be generated to an oncology target and that these VNARs can be site-specifically modified using a bio-conjugation technology developed by Almac Discovery.The aim is to build on this initial proof-of-concept research by combining Elasmogen's expertise in the generation and screening of VNAR proteins, with Almac Discovery's expertise in protein engineering and oncology drug discovery. The idea is to develop a modular VNAR ""plug-and-play"" platform for the accelerated development of innovative VNAR cancer drugs.Successful development of a platform technology that can overcome the limitations of full-length antibodies, and rapidly deliver VNAR therapeutic candidates with improved efficacy, will enable the full potential of these next-generation approaches to be realised and significantly improve human health."