CAR T (Chimeric Antigen Receptor T-Cell) is a type of cancer therapy that uses specially modified immune cells from a patient’s own body. T cells, a type of white blood cell, are removed from the patient and reprogrammed to find and attack cancer cells when reinfused into the bloodstream.
This advanced cancer treatment—now available in Lancaster at the Ann B. Barshinger Cancer Institute—was developed by work led at Penn Medicine in Philadelphia. Penn Medicine has been a global leader in groundbreaking immunotherapy research that includes CAR T. CAR T was the first gene therapy to be approved by the FDA and holds the promise of a new era of cancer treatment options.
Creating CAR T-Cell Therapy: How it Began
The groundwork for today’s immunotherapy was laid in 2003 with the mapping of the human genome. Scientists now knew which genes affected which traits in the body. Changing those genes would be more complex.
Over the next decade, Penn Medicine built on this knowledge, which led to the creation of CAR T-cell therapy.
Giving the Immune System a Boost
Without the boost from CAR T cells, it is difficult for the immune system to fight cancer on its own. Specialists from Penn Medicine focused their research on finding new ways to help the immune system do its job better.
Cancer spreads quickly because it starts from healthy cells in the body. When those healthy cells mutate and become malignant, the immune system fails to recognize them as something foreign to attack.
With CAR T-cell therapy, immune T-cells are taught to recognize cancer cells. A patient’s T-cells are genetically modified to find a specific chunk of biological code—the cancer fingerprint. When the T-cells are returned to the body, they hunt down and destroy all cells with that fingerprint. These engineered cancer-fighting cells are considered a “living drug,” remaining active in the body long as serial killers after the cancer is gone.
Penn’s Dr. Carl June Led the Way
Carl H. June, MD, one of the pioneers of CAR T-cell research, led the Penn Medicine team responsible for the historic FDA approval. In the early 1980s, June’s research was focused on bone marrow transplant (BMT), which is used to treat certain cancers of the blood. He was searching for ways to avoid a side effect of BMT called graft vs. host disease, in which the immune system of the donor (usually a sibling of the recipient) would attack the patient.
Dr. June wondered if it was possible to get the benefits of a BMT without the transplant, instead using the patient’s own immune system as a weapon again cancer.
Around this time, Dr. June served in the Navy, where he continued his research on bone marrow transplants. He also began studying T-cells in patients with HIV and AIDS and discovered he could take T-cells from a patient with AIDS, grow them in a lab, give them back to the patient, and the T-cell counts would improve. His ‘eureka’ moment came when he treated AIDS patients with CAR T cells for HIV, and realized those cells could survive in patients and multiply, without spreading HIV.
After he left the Navy, Dr. June came to the University of Pennsylvania and continued this approach in patients with leukemia, using the technologies he developed in his research for HIV/AIDS.
The First CAR T Patient
Bill Ludwig was the first patient treated with CAR T cells as part of a clinical trial at Penn’s Abramson Cancer Center.
Bill had been battling chronic lymphocytic leukemia (CLL) for nearly 10 years and had lost count of how many rounds of chemotherapy he had undergone. In 2010, out of options, David Porter, MD, his oncologist at Penn, enrolled him in a clinical trial for patients with his type of cancer.
Dr. Porter was leading the research and working with Dr. June. Bill would be the first to receive treatment, and the first to benefit!
Clinicians collected T-cells from Bill’s blood using a procedure called leukapheresis and sent those cells to the lab of Bruce Levine, PhD. The lab injected the T-cells with a virus that included the CAR gene, which became a part of the T-cells’ DNA. The cells continued to reproduce with a new receptor on their surface, making them capable of recognizing and destroying the cancer in Bill’s body.
Two weeks later, the cells had multiplied 700-fold, and were ready to be reintroduced to Bill’s blood stream, where they would grow even faster. Dr. Porter explains, “When they recognize there are cells to kill, it activates them to reproduce.”
After his last T-cell infusion, Bill became gravely ill due to cytokine-release syndrome—a strong immune response that causes high fever, low blood pressure and other symptoms. Against the odds, he survived. Doctors would later recognize this syndrome as a sign that patients are responding robustly to treatment and would develop protocols to safely treat it.
A month after his treatment, Bill had a bone marrow biopsy. The results were so astounding that a second sample was taken to make sure there was no mistake. The test detected no cancer in Bill’s body.
Bill remained cancer-free for 11 years, until his death from COVID-19 in January 2021.
Looking to the Future
Penn Medicine has used CAR T-cell therapy to treat hundreds of patients with cancer. It CAR T is now in clinical trials around the world, with variations that target many diseases. At Penn Medicine's Abramson Cancer Center alone, clinical trials have already led to FDA-approved therapies for lymphoma, leukemia and multiple myeloma. We hope to see similar results soon for glioblastoma, the most aggressive form of brain cancer, as well as other solid tumors. Thanks to the vision and dedication of these researchers, CAR T has revolutionized the Ann B. Barshinger Cancer Institute’s approach to fighting disease.