Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now, investigators have reported highly promising early results for CAR T therapy in a small set of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June, MD, and Daniel Baker, a doctoral student in Cell and Molecular Biology in the Perelman School of Medicine at the University of Pennsylvania, discuss this development in a commentary published today in Cell.

“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” said June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center.

T cells are among the immune system’s most powerful weapons. They can bind to, and kill, other cells they recognize as valid targets, including virus-infected cells. CAR T cells are T cells that have been redirected, through genetic engineering, to efficiently kill specifically defined cell types.

A new technique has been added to the CRISPR gene-editing toolbox. Known as PASTE, the system uses virus enzymes to “drag-and-drop” large sections of DNA into a genome, which could help treat a range of genetic diseases.

The CRISPR system originated in bacteria, which used it as a defense mechanism against viruses that prey on them. Essentially, if a bacterium survived a viral infection, it would use CRISPR enzymes to snip out a small segment of the virus DNA, and use that to remind itself how to fight off future infections of that virus.

Over the past few decades, scientists adapted this system into a powerful tool for genetic engineering. The CRISPR system consists of an enzyme, usually one called Cas9, which cuts DNA, and a short RNA sequence that guides the system to make this cut in the right section of the genome. This can be used to snip out problematic genes, such as those that cause disease, and can substitute them with other, more beneficial genes. The problem is that this process involves breaking both strands of DNA, which can be difficult for the cell to patch back up as intended, leading to unintended alterations and higher risks of cancer in edited cells.

Unnecessary playing with nature.

In January, Bennett’s doctors offered him the chance to receive a heart from a pig. He took it. “I know it’s a shot in the dark, but it’s my last choice,” he said in a press release from the University of Maryland Medical Center in Baltimore, where he was being treated. On 7 January, doctors transplanted the heart, which had been genetically modified so that the human body would tolerate it.

Bennett survived for eight weeks with his new heart before his body shut down. After his death, the research team learnt that the transplanted organ was infected with a pig herpesvirus that had not been detected by tests¹.

But even a few weeks is a long time for an animal organ placed in a human, known as a xenotransplant. Given that the human immune system begins attacking non-genetically modified pig organs in minutes, other xenotransplantation researchers are impressed with the experiment. “It’s actually beyond my expectation that the patient lived up to two months,” says Luhan Yang, a bioengineer and chief executive of Qihan Biotech in Hangzhou, China. “I think it’s a victory for the field.”