Poster Presentation Melbourne Immunotherapy Spring Symposium 2025

Modelling T cell immunotherapy response in colorectal cancer in vitro (#144)

Simon Manuel ST Tria 1 2 , Catherine CB Bond 1 , Kelly KO Olsen 1 , Terufumi TY Yoshida 1 3 , Bianca BN Nowlan 1 , Greg GK Kelly 1 , Vicki VW Whitehall 1 2 4
  1. Cancer, QIMR Berghofer, Brisbane, Queensland, Australia
  2. Faculty of Health, University of Queesnland, Brisbane, Queensland, Australia
  3. Colorectal surgery, Kansai Medical University, Hirakata, Osaka, Australia
  4. Pathology, Pathology Queensland, Brisbane, Queensland, Australia

Colorectal cancer is one of the most common forms of cancers with an equally high mortality rate. Early stage patients can expect a favourable outcome, however patients with metastatic disease have limited treatment options and dismal prognosis. Immunotherapy has revolutionized the care and outcomes for an array of different cancers, but this has thus far not been realized in colorectal cancers. Typically, immunotherapy studies are conducted in vivo, owing to their requirement of an intact immune system. However, these studies can be costly, time-consuming and often fail when they reach clinical trial stage. Patient derived organoids are 3-dimensional structures that maintain the molecular and morphological features of the originating tissue. Patient derived organoids have been shown to mirror the patient responses to different standard of care therapies, and even predict toxicity in healthy tissues. The Conjoint Gastroenterology Laboratory in QIMR Berghofer has established a pipeline with the RBWH that allows the collection of tissue and blood from colorectal cancer patients. The tissues are cultured to grow organoids that remain viable indefinitely and PBMCs are isolated from the blood. This has allowed us to create a growing biobank from an unbiased cohort of colorectal cancer patients. Using this biobank, I have established a model to co-culture organoids with autologous T cells. The T cells are trained to be cancer specific and validated using an array of flow cytometry and immunofluorescent assays. These assays examine markers for activation, exhaustion and function, as well as evaluate T cell mediated killing in real time. Our aim is to use this model to discover novel immunotherapeutic targets for colorectal cancer.