Releasing the Immune System Brakes: The Importance of Modelling Effects in Non-Clinical Safety Studies

The primary function of the immune system is to protect the body from infection by identifying and removing pathogens. A complex system, involving many individual cell populations, the immune system utilizes a range of mechanisms for the identification and subsequent removal of pathogens and other non-self material such as tumor cells. Due to the efficiency of the immune system, a range of control mechanisms serve to ensure that the potentially damaging effects of these killing mechanisms are directed specifically at pathogens, and resolved once the pathogen has been eliminated. Some of these control mechanisms utilize inhibitory pathways which mediate a negative signal to activated immune cells, instructing them to switch off. This is an important method of restricting an immune response to the period of infection only, enabling it to revert to baseline when the pathogen has been eliminated, and defects in this system can lead to hypersensitivity or autoimmune disease. It is now known that tumors exploit this system to prevent immune attack by upregulating expression of these inhibitory or ‘checkpoint’ markers to dampen the anti-tumor immune response.

Recently, this has become an area of interest for oncology. By blocking the negative signals mediated by checkpoint markers, and effectively taking the brakes off the immune system, increased anti-tumor activity can be induced. However, the complex nature of the immune system also means that any changes to its overall function can potentially lead to negative consequences, and a thorough understanding of the biology mediated by each checkpoint inhibitor product is essential in order to fully assess the risk of any unwanted effects.

Speaker

Kirsty Harper, PhD, MSc, BSc, Head of Biologics, Envigo

Kirsty leads the UK Biologics team, a role she has held since October 2017, having joined Envigo in June 2013. Throughout her time with the company she has supported customers by designing safety studies and non-clinical development programs for biologics in response to specific requests as well as providing scientific support and advice. Prior to this, she was employed as Principal Scientist at Oxford Immunotec Ltd, where she was responsible for pipeline product development projects and the provision of immunological advice and expertise.

Kirsty obtained her PhD in Immunology from the University of Bristol in 2005, after which she completed a post-doctoral position investigating peptide therapy as a potential treatment for autoimmune disease. She obtained her BSc and MSc degrees in Microbiology at Massey University in New Zealand and worked at the Malaghan Institute where she conducted basic research in autoimmune disease before emigrating to the UK.

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