How gene-edited New Zealand goats could help fight cancer

16

Gene-edited goats could make a big difference in the war against our biggest killer, New Zealand scientists have found.

Over recent decades, researchers have increasingly turned to antibodies – the main weapons of our immune system – to fight cancer.

While our immune system normally makes use of a large collection of antibodies that can target slightly different parts of a pathogen, one in particular is capable of recognising a single, specific target.

That’s made what are called monoclonal antibodies – or mAbs – exciting candidates for anti-cancer therapy, with the potential to exploit differences between cancer cells and normal ones.

One of the best-known examples today is breast cancer therapy Herceptin, designed to spot and bind to the HER2 proteins on the surface of cancer cells.

AgResearch senior scientist Dr Goetz Laible said mAbs continued to represent an important class of pharmaceutical proteins for the treatment of many serious human diseases, cancer among them.

However, therapies required the application of relatively large amounts of mAb for each patient – and getting that scale out of traditional lab-based methods wasn’t so easy.

“Mammalian cells need a highly controlled environment for their culture which causes high production and scale-up costs,” Laible said.

That’s where animals – capable of producing large amounts of these proteins in their milk – could speed things up.

In a new study, Laible and colleagues turned to transgenic goats – or those that have had a foreign gene deliberately inserted into their genome – to see if they’d make a suitable platform for cetuximab, an mAb commercially produced as Erbitux.

Genes holding the information for producing the mAb in milk were inserted into the genome of goat cells, from which the scientists produced live goats using the same technology made famous by the cloning of sheep Dolly.

“The additional genes in the genome enabled these goats to produce the antibody in their milk,” Laible said.

“Aside from this change in their milk, the goats involved are otherwise healthy, normal animals.”

His team were specifically interested to see whether the goats could not only make large volumes of the protein, but also whether it could be purified from the milk – and whether goat-produced mAb turned out to be fully functional.

Not only did the goats tick those boxes, but their mAb also appeared to be less immunogenic – producing less of an immune response – while packing attributes comparable with commercially available mAb produced in cultured mammalian cells.

Laible was excited at the prospect.

“A production platform for high-value therapeutic mAbs in goats would be especially attractive for New Zealand,” he said.

“Our animals have an excellent health status and are free of many harmful animal diseases that are common in many other countries.

“Adding New Zealand’s leading expertise in farm animal genetics and reproductive technologies, quality milk processing capabilities and efficient farming systems, this shows what an opportunity this could hold.”

The findings, published in preprint server bioRxiv, follow a slew of fascinating insights AgResearch scientists have gained through genetically engineering animals.

In 2018, they discovered a new way to knock out a major milk allergen by editing a cow’s genome.

They’re now using the latest GE tech to create New Zealand’s first “climate-smart” cow – boasting better milk production, greater heat tolerance, and fewer emissions – along with pigs that could make ideal organ donors for humans in the future.