Gene editing tool giving scientists an armour to fight solid cancers

Melbourne scientists have shown for the first time how a “revolutionary” blood cancer treatment could be tweaked to cure hard-to-treat solid ­tumours, including breast, colon and ovarian.

Melbourne scientists have shown for the first time how a “revolutionary” blood cancer treatment could be tweaked to also cure hard-to-treat solid tumours.

Solid tumours account for around 90 per cent of all cancers and include breast, colon and ovarian cancers.

In preclinical mouse model trials the Peter MacCallum Cancer Centre team used a genetic engineering tool called CRISPR to modify CAR T-cells giving them the ability to activate cancer-fighting immune proteins at the tumour site.

Chimeric Antigen Receptor (CAR) T-cell therapy trains a patient’s own T-cells and immune system to seek out and destroy their cancer.

Using the gene editing tool, which is like tiny molecular scissors, the Peter Mac team engineered CAR T-cell therapy to release special signalling proteins that boost the immune response.

Importantly, this was only at the tumour site which they believe may help make future treatments safer and more tolerable for patients.

Professor Phil Darcy is co-head of the Cancer Immunology Program at the Peter MacCallum Cancer Centre. Picture: Supplied

Co-senior authors Phil Darcy and Paul Beavis head the Cancer Immunology Program at the Peter Mac.

Professor Darcy said CAR T-cell therapy had been used in Australia since 2018 to treat blood-based cancers including various types of leukaemia, lymphoma and more recently multiple myeloma.

He said it had been a game-changer and can cure blood cancer patients who have run out of other treatment options, but the same results had not been achieved in solid cancers.

“Peter Mac is really part of a global scientific effort to solve this problem,” he said. “So as part of this global effort, work in our labs in preclinical models and patients has shown there are several key criteria we needed to overcome to make these CAR-T cells work (in solid tumours).

“We need better approaches to enable the CAR-T cells to survive in the patient and we need to overcome the tumour-like environment and its capacity to dampen or suppress CAR-T cell activity.

“And we need CAR-T cells to be able to trap it and penetrate the tumour in high numbers to have an effect.”

Professor Paul Beavis says the results show that the technology has a lot of potential. Picture: Supplied

Professor Beavis said work by other groups had shown the potential of improving CAR-T cell therapy to treat other cancers by engineering them to express a second gene called armour.

“These are naturally found in the body, they cause inflammation, and so in the context of cancer, they can be used to activate the immune cells to make them better at fighting the cancer,” he said.

“We tested this new technique in multiple cancer models such as breast, colon and ovarian cancer and the results were incredibly promising with cure rates close to 100 per cent.”

The scientists cautioned this approach has been seen to work in mouse studies and the aim now is to progress to the first human trials in the next few years.

Professor Darcy said as the system the team developed allowed for the immune response to be localised to the tumour, they expected to see less toxicity which should result in a safer treatments.

“In animal models, this targeted strategy led to improved tumour control and long-term survival, even in models where human cancers were introduced.”

The Peter Mac team tested the new technique in multiple cancer models and said the results were “incredibly promising” with cure rates close to 100 per cent. Picture: Supplied

The results were published in a Nature paper on Wednesday, and described as “remarkable”.

“The results emphasise that this technology, we believe, has a lot of potential because it can be applied to any type of CAR-T cell, meaning that it could be applicable to multiple different cancer types,” Professor Beavis said.

Funding for the research included grants from the National Breast Cancer Foundation. Its executive director Dr Julie Ince-Demetriou said with breast cancer remaining the fifth leading cause of cancer death in Australia, this promising discovery will provide hope to many people.

Originally published as Gene editing tool giving scientists an armour to fight solid cancers