by SHELLY FAN
Ask a cancer researcher what the breakthrough treatment of the decade is, and they’ll tell you CAR T takes the crown.
The therapy genetically engineers a person’s own immune cells, turning them into super soldiers that hunt down cancerous blood cells. With astonishing speed, multiple CAR T therapies have been approved by the FDA for previously untreatable blood cancers. So far, over 15,000 patients have been treated with the therapy.
To Dr. Carl June, a pioneer of the technology at the University of Pennsylvania, we’re only scratching the surface of CAR T’s potential.
In a perspective article published in Nature this week, June and colleagues laid out a path forward.
At its root, CAR T therapy taps into the natural “killer instinct” of a type of immune cell, called a T cell, and directs it to a particular target—for example, blood cancer cells. But with careful redesign, CAR T therapy can be genetically engineered to tackle a wide range of humanity’s most prominent medical enemies: autoimmune diseases, asthma, and heart, liver, and kidney diseases caused by increasingly stiffening muscles.
Even more intriguing, CAR T may help clean out senescent “zombie” cells, which are linked to age-related diseases, or combat HIV and other viral infectious diseases.
“We are only beginning to realize the full potential of this living drug,” said the authors.
What’s CAR T Again?
CAR T stands for “chimeric antigen receptor T therapy.” I like to think of it as a Mr. Potato Head with plug-and-play parts.
The core “potato” is the immune T cell, a family of cells that normally survey our bodies to seek out and destroy invaders such as cancer or infections. Add to this CAR “parts”: genetically engineered protein “hooks” that can grab onto a specific protein on a diseased cell.
CAR T was first developed to battle HIV—with lackluster results—but it rose to prominence for its efficacy at treating blood cancers. Here’s how it usually goes: a patient’s T cells are isolated from a blood draw and genetically enhanced with CAR protein constructs in the lab. After being infused back into the body, the super-soldiers evade tumor cells’ defenses, with a single engineered cell killing hundreds if not thousands of cancerous enemies.
CAR T is truly “a new pillar of therapy,” said the authors. With T cells involved in other diseases, can the therapy do more?
A Solid Struggle
The first move to expand CAR T beyond blood cancers is targeting solid cancers—think pancreatic, breast, colon, and others. Sadly the results have “largely been disappointing” in multiple clinical trials so far, said the authors.
But from these failures, we’ve learned tons. Unlike blood cancers, solid tumors build a local biological “fortress” and pump out chemicals that hold T cells at bay and dampen their destructive activity. One idea to help them break through is directly injecting CAR T cells into tumors. Another is to use CRISPR to equip CAR T cells with a genetic profile—adding or deleting certain genes—that evades these defenses.
Unfortunately, other barriers remain. Solid tumors are often composed of an amalgam of cells, each with its distinct fingerprint of surface proteins. This makes it difficult for a single CAR T design to hunt down all cancerous cells. Some protein targets, called antigens, also dot the outside of healthy cells, causing collateral damage.
Singularity Hub for more