The promising immunotherapy treatment giving blood cancer patients hope – if they can afford it

CAR-T treatment involves removing a patient’s immune cells, re-engineering them to attack the cancer, then returning them via an infusion. Photo / Getty Image

Cancer treatment is changing. While chemo and radiotherapy aren’t likely to go away any time soon, medical scientists are focused on arming the body’s own immune cells to fight off threats. One cutting-edge treatment offering new hope for patients is CAR-T. It has already had success with patients suffering
from blood cancers and there are signs it may even be effective for autoimmune disorders, with early clinical trials putting participants into remission.

Actor Sam Neill’s declaration that he is now free of lymphoma, a form of blood cancer, after participation in a CAR-T trial in Australia made global headlines last month.

However, there are problems with CAR-T, which involves removing a patient’s immune cells, re-engineering them to attack the cancer, then returning them via an infusion. For a start, the treatment is extremely expensive. In the US, where it has been used for several blood cancers, the cost of the cells alone can range up to almost US$500,000. Plus, the potential side effects are serious, some patients respond initially then relapse, and there is a risk of the immunotherapy treatment causing secondary cancers.

At Wellington’s Malaghan Institute, researchers are working on making the treatment safer and more effective, in the hope it will be part of the future of medical care in New Zealand. “We want something that is made in New Zealand and accessible to New Zealanders,” says Rachel Perret, who leads the research programme.

Currently her team is midway through a groundbreaking clinical trial, ENABLE-2. So far, 30 patients with B-cell non-Hodgkin lymphomas have been treated using CAR-T cells engineered here, and the aim is to treat another 30 by the end of the year. Collaborating with researchers in Guangzhou, China, the cells that have been developed can be delivered as a one-off outpatient treatment, and results from a smaller initial trial suggest at least some patients will go into long-term remission.

“The main reason for relapse or failure to respond is that the cancer is crafty and constantly changing,” says Perret. “Sometimes when we target one protein on the cancer, we drive it to become resistant.”

More advanced immunotherapies are being developed that engineer a patient’s T-cells to recognise several different proteins simultaneously. This makes it more difficult for the cancer cells to avoid attack.

Another potential reason the treatment might not work is the CAR-T cells can become exhausted. “We know part of the exhaustion is our fault,” says Perret. “When we take the cells out of a patient’s blood and grow them into CAR-T cells, we have to put a pretty strong push behind them to make them activated and divide into large numbers. Then, when we put them back in the body, they face a fight with the cancer, which is pumping out chemicals and expressing proteins on its surface that are all designed to avoid the immune system and combat it. Those things combine to make the CAR-T cells burn out.”

Sam Neill: Cancer-free after participation in CAR-T trial in Australia. Photo / Getty Images

Malaghan researchers are looking at modifying the way they grow and stimulate the CAR-T cells, to make the period of time they are outside the body shorter and less tiring. There are also technologies that can knock out the genes that control T-cell exhaustion.

“It can make the cells sort of super soldiers, resistant to all the negative signals that could cause them to become exhausted,” says Perret.

Potentially serious side effects of the commercial CAR-T therapies available overseas include neurotoxicity and cytokine release syndrome. So far, the CAR-T cells being manufactured by the institute’s partner, BioOra, for use in trials have had a much better toxicity profile.

“We’ve also designed and built what we call a safety switch,” says Perret. “It’s an additional protein we add to the cells so if they did get problematic because they were too active and pumping out dangerous cytokines, or if the CAR-T cells themselves turn into a cancer, then we’ve got that extra protein tag and we could treat the patients with a readily available, standard drug that would wipe them out.”

Blood cancers have been the easiest target for CAR-T cells; solid tumours are next.

BioOra, a business that spun-out from the Malaghan Institute, is building a manufacturing plant in Christchurch where it can produce at scale and hopefully make the treatment more accessible and affordable.

“We’re very optimistic that this trial will be successful,” says Perret. “The exciting thing is we’re doing it here in New Zealand.”

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