Understanding how changes in immune cells over time contribute to cancer therapy success

Chee J, Nowak AK, Lake RA, WJ Lesterhuis, A Chopra, M Watson, R Holt, A Zaitouny, E De Jong, D Correa, J Kidman, N Principe

Funding: icare Dust Diseases Board, Cancer Council WA

Synopsis: Malignant mesothelioma is an incurable cancer caused by asbestos. The standard treatment for mesothelioma is chemotherapy, but outcomes remain poor. Because immunotherapy is an exciting option to improve mesothelioma treatment, and our laboratory work supported combining chemotherapy with immunotherapy, we recently completed a clinical trial in which 54 patients with mesothelioma received this novel combination (chemo-immunotherapy). We observed deep and durable responses, suggesting that immunotherapy may work better when combined with chemotherapy. However, the treatment did not work for everyone.
This project aims to understand the mechanisms behind why some individuals respond to chemo-immunotherapy but others do not, to develop novel methods of predicting these responses, and to identify ways to enhance responses. We have collected blood samples from patients before and during trial treatment and will compare individuals who responded well to those who did not. We will characterise millions of genes from these samples, apply cutting-edge mathematical methods to visualize and identify the patterns of change over time that can predict successful treatment outcomes.
This combination chemo-immunotherapy is so promising for mesothelioma that we are initiating a 480 person randomised phase 3 trial. However, understanding who will respond well to treatment, and who may need additional or different strategies, will be key to improving patient outcomes further. This project will identify early markers of treatment outcomes, which we will be able to validate in the randomised phase 3 trial. Eventually, we may be able to better understand how to alter or add to treatment to improve patient survival.

NCARD Research Team

Jonathan Chee, Richard Lake, Anna Nowak, Joost Lesterhuis.

Students: Nicola Principe (PhD 2019-), Joel Kidman (PhD 2019 – 2023)