Here’s how we can bring the potential of cell therapies to more cancer patients

Imagine a person living with blood cancer whose disease has returned and progressed after multiple rounds of treatment, leaving no further options. Now, imagine a world in which scientists can isolate this patient’s T cells (immune cells) and modify them in a lab to create a ‘living medicine’ that can recognize and attack their specific cancer cells.

This scenario may sound a little like science fiction, but it is in fact real science that has come to fruition and is being explored further. These engineered cells are called chimeric antigen receptor T cells (CAR-Ts). The first CAR-T therapies for blood cancer were approved by the US FDA in 2017. Since then, cell therapies have been approved across multiple blood cancers and are being explored as a potential option for many patients for whom other treatments have been exhausted, as well as for those with a newly diagnosed disease.

This World Cancer Day (4 February), we recognize all who have faced cancer and acknowledge the great strides made in the research and development of cancer treatments with the aim of improving outcomes and increasing the chances of finding cures.

To date, CAR-Ts have shown efficacy in blood cancers; however, extending this success to solid tumours has proved challenging. Additionally, the process of creating a CAR-T therapy is complex and time-consuming. At AstraZeneca, we are committed to exploring new strategies to effectively target solid tumours and create ‘off-the-shelf’ cell therapies with the aim of bringing the potential of cell therapy to more patients.

In blood cancers, cancerous cells freely circulate in the bloodstream, making them more accessible to targeting with cell therapies. In contrast, cell therapies are currently less effective against solid tumours, which comprise about 90% of all cancer diagnoses, because of the ecosystem that surrounds the cancer cells inside the body. This ‘tumour microenvironment’ poses physical, metabolic and immunological barriers to treatment. To increase their potential effectiveness in solid tumours, cell therapies must be designed to overcome these barriers.

At AstraZeneca, our scientists are developing next-generation, ‘armoured’ CAR-T therapies by engineering T cells to express additional proteins that help them to survive and function more effectively in the tumour microenvironment. For example, armoured CAR-T cells can be engineered to express proteins that attract other immune cells to the tumour site, as well as proteins that break down physical barriers in the tumour microenvironment and enable CAR-T therapies to penetrate the tumour more easily.

We’re also advancing T cell receptor therapies (TCR-Ts) through our acquisition of Neogene Therapeutics. TCR-Ts are next-generation approaches that are showing potential in the treatment of solid tumours. They can be engineered to recognize and kill tumour cells that express specific genetic mutations while leaving healthy cells untouched. Unlike CAR-T therapies, which recognize proteins expressed on the surface of cancer cells, TCR-Ts can identify targets inside the cells, expanding the breadth of targets accessible by cell therapies.

The majority of cell therapies currently being investigated in the clinic are customized for each patient and require a specialized infrastructure, making them costly and time-consuming. CAR-Ts are manufactured by isolating a patient’s T cells, engineering them in a lab and reinfusing them into the patient, a process that can take weeks or even months, delaying urgently needed treatment. Currently, the manufacturing cost of cell therapy is upwards of $100,000 per patient. In addition, the current manufacturing capacity for approved CAR-Ts is much less than the number of patients with the cancers they are designed to treat and the number of centres that can prescribe CAR-Ts is limited due to their specialized nature, with only 188 centres in the US at present. These issues, combined with the task of collecting enough cells from a patient to produce an effective cell therapy (which is not always possible, as patients with cancer often have weakened immune systems and depleted T cell numbers), have created challenges for researchers striving to scale the potential of cell therapy.

To overcome these challenges, we and others are developing next-generation cell therapies that utilize T cells from donors, rather than patients. This approach, known as allogeneic cell therapy, can allow us to create a library of ‘off-the-shelf’ therapies with the aim of manufacturing them at scale so they are more readily available than individual, patient-specific cell therapies. However, there are challenges with ensuring they are tolerable and effective.

One of the challenges is preventing graft-versus-host disease (GvHD), a severe and life-threatening condition in which the donor T cells attack the healthy cells in a recipient’s body, rather than just the tumour cells. Another challenge is correctly matching the donor cells to the recipient’s cells; if they are mismatched, then the patient’s immune system may attack and reject the treatment, rendering it ineffective. At AstraZeneca, we are developing innovative ways to engineer donor cells to address immune rejection and reaction.

The science of cell therapy has come a long way, but there are far too many patients still waiting for breakthroughs that could potentially alter the course of their cancers. At AstraZeneca, this knowledge drives our bold ambition to one day eliminate cancer as a cause of death. We know that in order to achieve this goal, we must attack cancer from multiple angles – and that includes advancing the next generation of cell therapies with the aim of making them more effective and accessible. By following the science, we can help close treatment gaps and aim to bring these innovative treatments to many more patients in the future.