CAR-T Cell Therapy May Cause Cancer, FDA Warns

CAR-T cell therapy is considered a cutting-edge cancer treatment. However, the US Food and Drug Administration (FDA) is investigating if it can cause secondary cancers six years after approving the treatment.

FDA On CAR-T Cell Therapy

The FDA is looking into incidents when patients who had a certain type of cutting-edge cancer treatment, CAR-T cell therapy, went on to have additional cancers. CAR-T cell therapy, the course of treatment, entails taking out certain immune cells from patients, known as T cells, and genetically altering them to target and eradicate cancer.

Since viruses can naturally enter cells, scientists employ them to transfer and insert new genetic material. However, the possibility that these viruses could unintentionally start another cancer has long been regarded as theoretical. The FDA stated that patients' development of secondary malignancies may have been influenced by their use of these viruses.

Using viruses has the drawback that their genetic cargo often finds a random spot in the genome of the host. Depending on where it integrates, this new genetic material may trigger a nearby cancer gene.

"The concern would be that somehow the new genetic material that you put into patients' T cells can induce cancer in that cell, perhaps by where it gets inserted in the DNA," said David Porter, an oncologist and expert in blood cancer at the University of Pennsylvania School of Medicine, where researchers developed CAR-T cell therapy.

The FDA mandates that patients receiving CAR-T cell therapies have follow-up monitoring for 15 years following therapy due to the said risk. The agency also suggested that patients and clinical trial participants receiving CAR-T cell therapies should be monitored life-long for new malignancies.

Maksim Mamonkin, an associate professor of pathology and immunology at Baylor College of Medicine, who is also involved in numerous clinical trials of CAR-T cell therapies, admitted that he was unaware of any instances in which modified T cells developed into malignancy. However, he claims that no therapy is risk-free, so the report from the FDA is not entirely impossible. He added that the possibility that the CAR gene accidentally ends up in the wrong place in the genome cannot be ruled out.

Another theory is that side effects from earlier cancer therapies, such as radiation and chemotherapy, caused patients' new T-cell malignancies. In addition to killing cancer cells, these medicines harm DNA in healthy cells. By doing this, they may alter cells in a way that subsequently results in cancer.

"Very often, cancer is more than just one mutation, more than one insult," Porter added. "So you may damage the DNA with prior chemotherapy or radiation, making that cell more prone. Should it have another event, then it's well on the way already to becoming a cancer cell."

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CAR-T Cell Therapy

Six commercial CAR-T cell treatments targeting blood malignancies, such as lymphomas and leukemias, have received FDA approval since 2017. Researchers are also testing these promising treatments for autoimmune disorders and various other malignancies.

When more traditional medicines like radiation and chemotherapy are ineffective, these therapies are the last resort. CAR-T cell therapies have demonstrated impressive outcomes against some of the most incurable malignancies, even though they don't always result in a cure.

Depending on the type of cancer, up to two-thirds or more of patients have experienced remission following CAR-T cell therapy.

When Kymriah, the first CAR-T cell therapy, was approved six years ago, it was hailed as a milestone. Debuting at an astounding $475,000, Kymriah is priced similarly to more newly approved CAR-T cell therapies.

Porter, however, was taken aback by the FDA statement.

"We have not seen this at Penn," he said, referring to cases of T-cell cancers developing after treatment.

Using CAR-T cell therapies manufactured at Penn and hundreds more using over-the-counter medications, the institution has treated over 800 individuals.

Chimeric antigen receptors (CARs) are surface proteins produced by patient T cells with genetic material added to them in a lab. These CARS detect and bind to specific proteins on the surface of cancer cells, turning the patient's cells into cancer assassins.