Scientists are claiming “extraordinary” success with engineering immune cells to target a specific type of blood cancer in their first clinical trials.
Among several dozen patients who would typically have only had months to live, early experimental trials that used the immune system’s T-cells to target cancers had “extraordinary results”.
In one study, 94% of participants with acute lymphoblastic leukaemia (ALL) saw symptoms vanish completely. Patients with other blood cancers had response rates greater than 80%, and more than half experienced complete remission.
Speaking at the annual meeting for the American Association for the Advancement for Science (AAAS), researcher Stanley Riddell said: “This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients.”
To administer the T-cell therapy, doctors remove immune cells from patients, tagging them with “receptor” molecules that target a specific cancer, as other T-cells target the flu or infections. They then infuse the cells back in the body.
“There are reasons to be optimistic, there are reasons to be pessimistic,” said Riddell, of the Fred Hutchinson Cancer Research Center in Washington state. He added that the researchers believe that lowering the dose of T-cells can reduce the risk of side-effects.
“These are in patients that have failed everything. Most of the patients in our trial would be projected to have two to five months to live.”
Even more hopeful was researcher Chiara Bonini, who said she has not seen remission rates like those of recent trials in over 15 years. “This is really a revolution,” she said.
“T-cells are a living drug, and in particular they have the potential to persist in our body for our whole lives.”
Bonini, a haematologist at San Raffaele University in Milan, said that in another study researchers had tracked the presence of “memory” T-cells for two to 14 years after they had been introduced into cancer patients for whom bone marrow transplants had failed to work.
“This is a living therapy,” Riddell said. When you put it in the cells will undergo expansion in vivo.”
Tests so far have only targeted certain blood cancers, and the researchers acknowledged they needed to work on tumors and track how long patients would remain in remission. Cancer cells can sometimes hide unnoticed by the body’s defenses, or simply overwhelm them and throw the immune system into overdrive.
T-cell therapy is often considered an option of last resort because reprogramming the immune system can come with dangerous side-effects, including cytokine release syndrome (sCRS) – and overload defense cells. Twenty patients suffered symptoms of fever, hypotension and neurotoxicity due to sCRS, and two died, but the researchers noted that chemotherapy had failed in all the patients who participated in the new trials.
Riddell hesitated to say when the work would move beyond limited trials, but Bonini said: “I think we’re very close to some cellular product.”
She also expressed hope that the modified memory T-cells could eventually provide a long-term defense against cancer, using cells that “remember it from 10 years earlier, and kill it so quickly you don’t even know you’re infected”.
In the most promising study, about 35 patients with ALL were treated with Cars-modified T-cells; 94% went into remission, though symptoms could reappear. More than 40 patients with lymphoma have also been treated, with remission rates of more than 50%. In a group with non-Hodgkin’s lymphoma, there was evidence of diminished cancer symptoms in more than 80% of cases.
“Much like chemotherapy and radiotherapy, it’s not going to be a save-all,” Riddell said of the new therapy, adding: “I think immunotherapy has finally made it to a pillar of cancer therapy.”
A paper on the ALL research is currently under review and pending publication.
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Cancer researchers claim 'extraordinary results' using T-cell therapy
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