How cell therapy is helping to engineer cancer treatments
The human body’s immune system is a remarkable thing: our white blood cells can fight off viruses, bacteria, all but the most virulent invaders. But when it comes to tackling cancer, they struggle: cancer cells are, from their perspective, part of the body. For decades, scientists have been working to reengineer T-cells, adding chimeric antigen receptors (or CARs) to attack cancerous cells. “Zelig Eshhar and Gideon Gross described the first successful generation of a CAR-T cell in the lab 30 years ago,” explains Markwin Velders, vice president of operations at Kite Pharma, a Gilead company, one of many working on this type of cancer treatment. In November 2018, the first NHS England patient was treated with CAR-T therapy, marking the culmination of decades of research.
CAR-T therapy is a complex process: first, a patient’s white blood cells are removed and, where necessary, shipped to a specialised laboratory in temperature-controlled containers. The T-cells are then separated out, and a new gene is introduced – a molecule receptor to recognise target cancer cells. The re-engineered cells are then multiplied, ready to be infused back into the patient. As CAR-T is an individualised treatment, traceability is paramount. “We need to know where the cells are at all times. It’s a chain of identity: they must only get their own cells back,” says Velders. Continued discovery Sam Chivers Harnessing the body’s own immune response inevitably carries risks. “If we start activating T-Cells, they start releasing cytokines to attract other T-Cells – so you create an inflammatory environment,” explains Velders. That inflammatory response, known as cytokine release syndrome, is a sign that the treatment is working – but side effects can be severe. “This is an intensive therapy, and patients may get quite sick. A proportion will even require intensive care,” explains Claire Roddie, a consultant haematologist at University College London Hospital, one of the UK hospitals conducting research into CAR-T therapies. Physicians are still learning how to control those side effects and designing next-generation treatments to enable greater precision in treatment".“Say for instance, you want to tune down your CAR activity because of toxicity, well, you could [theoretically] do that with a drug switch,” says Roddie, though she emphasises “Those are all in the research domain.”Risks are also being monitored using disease registries.The future Sam Chivers So far, in practice, CAR-T therapy can only be used to treat certain blood cancers and does not work for all patients. From a technical perspective, blood cancers are simpler: they’re easy to access and express a clear target protein. “We know solid cancers are much more difficult,” says Roddie, but eventually, “our goal would be to take this approach and apply it across the board to all sorts of solid tumours.”At present, the industry continues to learn more about the management of CAR T cell therapy. “We’re pushing for the data to be registered properly, including PROs (patient reported outcomes), and also to harmonise the way it is being collected," says Natascha Bolanos, Europe regional manager for the Lymphoma Coalition, a patient advocacy group. That reflects a larger obstacle: for an industry used to churning out standardised treatments, CAR-T presents new challenges. “It's not only a new way of treating patients, it's a new class of therapies,” says Velders. “For doctors, patients, regulators, for everyone – this is still new.”“It’s very exciting,” says Bolanos. “But we still have a lot to discover: about cell therapy, about the diseases, about how to make sure patients are receiving therapies in the best way possible.”--This article was funded by Kite, a Gilead company000/IHQ/19-03//1306Date of preparation: April 2019