A disease-slaying drug that lives on in the body?

CAR T cells have been shown to eliminate malignant tumors in patients who faced all but certain death. A new study suggests that cells as medicine could have applications well beyond cancer.

A pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response.National Institutes of Health

A rogue cell. That’s the problem in cancer.

Trillions of cells compose our organs and tissues. How can something so normal, so innocuous, so essential, become a culprit? When a patient presents with cancer, it can mean unbearable pain, exhaustion, or even major organ malfunction. At the root of this tangle of symptoms is a cell that has acquired mistakes in its DNA. For centuries surgeons have sought to excise these cells and for decades drugs have been designed to kill them. Unfortunately, cancer has largely prevailed.

A little over a decade ago, our group tested a simple idea: Could we fight cancer cells using cells that we changed? We armed these killer immune cells — T cells — with a tailor-made receptor so they could see and kill cancer. This treatment, called CAR T therapy, worked even better than we could have hoped.

Patients had pounds of cancer disappear over the course of a few weeks. CAR T therapy has cured cancer patients who were on death’s doorstep. These cells didn’t only kill the cancer but remained on patrol in the body for years, marking them as the first living drug. This approach ushered in a new paradigm of cells used as medicine. Their remarkable effects on cancer led, in 2017, to the first-ever approval from the Food and Drug Administration for a genetically engineered cell therapy. There are now six FDA-approved cancer treatments using CAR T cells, and there are hundreds of trials underway globally to apply CAR T therapy to other cancers. It is a medical revolution.

The results have been breathtaking. Previously, cancers were thought to be treated, not cured. However, earlier this year we marked the 10th anniversary for our first patients whose cancers disappeared with no trace of return. This living drug offers hope where none existed. It also presents its own unique challenges. CAR T cells are fantastic cancer killers, but eliminating pounds of cancerous cells in a short time can have side effects. In severe cases, patients can experience low blood pressure, high fevers, and even multiple organ failure. Physicians are learning how to manage these side effects, and the safety of this therapy remains a concern.

Then there is cost. Current treatments, along with hospital stays, can cost hundreds of thousands of dollars per patient. This puts the therapy beyond the reach of most cancer patients. Multiple approaches are underway to improve the safety and efficacy and to reduce the cost of this therapy.

The documented successes of CAR T therapy have thus far been limited to blood cancers. Now, a decade after the initial trials in cancer, a group in Germany has reported the first clinical trial using CAR T therapy to treat a life-threatening autoimmune disease. Five young adults with a severe form of lupus were treated with CAR T cells designed to kill diseased immune cells. Every patient saw a resolution of their symptoms and was declared to be in remission. The effects were so stark that these patients were taken off the immunosuppressive drugs that had been required to manage their disease.

Have these patients been cured, or is this only a temporary fix? The long-term effects are as yet unknown, but a handful of the patients who were treated earliest have remained symptom-free for more than a year. What’s more, none have exhibited severe side effects. We think this may be because the number of cells being targeted in lupus is dramatically lower than in cancer. These results are still early. A larger trial confirming the findings is planned. Nevertheless, this is a landmark study and indicates that this living drug has potential beyond cancer.

These striking clinical results suggest that engineered cells likely have much broader treatment potential than has been understood. Already, scientists have used this living drug to treat infectious diseases such as HIV and invasive mold infections. CAR T cells have also been engineered to kill scar tissue in failing animal hearts to restore heart function. Cardiac scarring is implicated in nearly every form of heart disease, which is one of the most prevalent killers in the world. CAR T cells have also been generated to kill senescent cells. Researchers have discovered that CAR T cells in mice could kill these zombie-like cells to treat a serious form of liver disease.

Such successful applications of CAR T therapy in animals suggest that a wide range of conditions may one day benefit from this living drug, including respiratory diseases, rheumatoid arthritis, multiple sclerosis, muscular dystrophy, Alzheimer’s, and possibly even the pathophysiology of aging.

Much remains unknown, but one thing is clear: We are only at the beginning.

Daniel Baker is a PhD candidate at the University of Pennsylvania and an authority on the diverse applications for CAR T therapy beyond cancer. Carl June is director of the Center for Cellular Immunotherapy at the University of Pennsylvania and a pioneer in the field of CAR T therapy. He led the development of the first FDA-approved cell and gene therapy and is scientific cofounder of Tmunity and Capstan.