Carina Biotech scientist Dr Veronika Bandara presented data at this week’s Eradicate Cancer Conference on Carina’s latest CAR-T cab off the rank that has demonstrated significant killing of two colorectal cancer cell lines in vitro and complete tumour elimination in a pre-clinical colorectal cancer model.
The CAR-T cell was also shown to be highly cytotoxic against two neuroblastoma cell lines.
These cancer-busting CAR-T cells are targeted at LGR5 (leucine-rich repeat-containing G-protein coupled receptor 5) – a cancer stem cell marker that is abundant in solid tumours and particularly highly expressed in colorectal cancer and metastatic colorectal cancer.
Dr Bandara said: “We designed and built six different CAR constructs based on an anti-LGR5 antibody. Four of the constructs showed fantastic cytotoxic activity against the LoVo and LIM1215 colorectal cancer cell lines in vitro. The same constructs were highly cytotoxic against the two neuroblastoma cell lines SHY-5Y-SY and BE-2-ME.”
Carina Biotech’s CEO, Dr Deborah Rathjen said: “The data to be presented by Dr Bandara this week is very promising, and suggests that this CAR-T cell is a potential therapeutic for colorectal cancer. The benefit of targeting a cancer stem cell marker is that we can get to the core of some cancers, in this case cancers expressing LGR5. We often see patients, for example with colorectal cancer, go into remission after first-line treatment only for their cancer to return, we think, due to the fact that the cancer stem cells are somehow resistant to traditional anti-cancer therapies.”
Dr Bandara said: “The next steps will be to further validate the LGR5 CAR-T cells in multiple pre-clinical animal models and against patient-derived tumour samples. We will also confirm safety of the LGR5 CAR-T cell by testing against normal tissues and by undertaking other safety evaluations. We will also work towards a TGA-approved manufacturing protocol to produce CAR-T cells for first-in-human clinical trials.”
This is Carina’s latest CAR-T cell candidate in a growing pipeline, underpinned by its proprietary platform that produces “supercharged” CAR-T cells.
The research is being conducted in conjunction with a $750,000 grant from the Government of South Australia’s Research, Commercialisation and Startup Fund (RSCF). www.innovationandskills.sa.gov.au/rcsf