Our own cells could be the secret weapon in the fight against cancer

Rami Niemi

What if you could endow cells with new functions? What if you could train them to deliver drugs inside the body at will? This will happen sooner than you think. We are in the midst of an accelerating revolution in medicine based on cell therapy. In 2020, we will be able to use genetic engineering to modify cells and use them to deliver drugs such as antibodies and other proteins. This signals a shift from the conventional paradigm of drugs that must be taken continuously – to cells that mimic drugs and continuously make the drugs inside the body.

The technology now exists to deliver genes encoding antibodies or proteins to cells. In fact, the first gene therapy approved by the US Food and Drug Administration was a modified T lymphocyte that allows targeted killing of cancer cells. Now, think about cells that can be gene engineered to survive for an extended time inside the body, travel to the site of disease, sense when they have arrived, and deliver cargo like so many endless microscopic drones making pharmacy deliveries. We will be able to use cells rewired as medicines to treat cancer or diabetes.

Off-the-shelf biologic drugs, such as antibodies that function as immune checkpoint inhibitors or bispecific antibodies that link immune cells to cancer cells, are now regularly used to treat several types of cancer. However, they must be administered repeatedly, are expensive, do not spread to all the sites of cancer in the body and do not induce clinical responses in a significant percentage of patients.

Other drugs, such as insulin for the treatment of diabetes, must be injected around the clock for a lifetime or patients must wear an infusion pump. Next year we will find ways around these challenges, by using technology to modify cells from patients, or potentially in some cases, from donors to deliver the sites of disease in a patient’s body.

How cells may be differentiated, programmed, unprogrammed, and reprogrammed to produce drugs is the fruit of decades of basic and translational research. One technique starts with stem cells that, when cultured in a lab with instruction factors, differentiate and mature into the cells that produce insulin. In cancer, another technique for cell therapy starts with mature immune cells (T cells) and genetically modifies them to express a sensing receptor – a chimeric antigen receptor, or CAR – on their surface that can detect, and trigger the destruction of, cancer cells.

The next generation of cell therapies that we will see in 2020 combines the above technologies with gene modification as a means of controlling the production of drugs on demand. To visualise this control, think of light switches. The first generation was a simple on/off switch; next, we had dimmers allowing adjustable light on demand; then motion sensing lights; and now voice-controlled lights.

By adding Boolean “and/or/not” switches to cells, scientists can wire in continuous production, conditional production, or a halt in production of a therapeutic antibody or protein. Teams at the University of Pennsylvania, Massachusetts General Hospital and the Memorial Sloan Kettering Cancer Centre in New York have separately found ways to use this technology to programme cells to produce cancer-fighting antibodies.

The implications of emerging cellular drug therapies go beyond the science. For a limited series of infusions with durable or lifetime benefit, payment and reimbursement is evolving, especially in multi-payer countries such as the United States where patients often change insurance carriers when changing jobs. We also will face questions about how drug regulations should be revised and adapted to expedite these advances. To realise the full potential of cells as medicines we must adapt to the new paradigm for the benefit of patients.

Bruce Levine is the Barbara and Edward Netter Professor in cancer gene therapy at the University of Pennsylvania

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