A living drug, called CAR-T cell therapy, has revolutionized the treatment of blood cancers, achieving thousands of complete remissions of leukemias, lymphomas and myelomas since its first experimental use in 2010. The therapy involves extracting immune cells from the patient, genetically modifying them, and then reintroducing them, now with an enhanced capacity to destroy cancer cells. However, this successful treatment has so far failed against solid tumors, which are the most common kind. A new study released Thursday offers hope. An ultrasensitive version of CAR-T cell therapy has successfully eliminated human pancreatic, ovarian and kidney cancer tumors implanted in laboratory mice.
The lead researcher is the French-Canadian immunologist Michel Sadelain, born in Paris 66 years ago. His team demonstrated in 2003 that CAR-T cells, which target the CD19 protein on the surface of cancer cells, eliminated lymphomas in mice. Solid tumors—such as those of the breast, lung, colon, or pancreas—are more heterogeneous and do not display the CD19 protein, which has led to the failure of this strategy over the past two decades.
Sadelain’s group at Columbia University in New York is proposing a new target: the CD70 protein, characteristic of more than 20 types of solid tumors. It’s a well-known target, but until now no experimental treatment had worked because it’s apparently present in only a percentage of the cancer cells within a given tumor. One of the researchers on the Columbia team, Sophie Hanina, had a hunch: perhaps the CD70 protein was indeed present in all tumor cells, but in some of them at such minute levels that it was undetectable by standard CAR-T cell therapies.
The main downside to CD19 targeting CART is that it kills all B cells. Since CD70 is on T and B cells you'd end up with a really poor immune system without some sort of kill switch built in. CD70 also has high expression in the liver and expresses in bone, cartilage, and skeletal muscle.... you can avoid that in mice because its likely different enough but I think they'd be really lucky if this passed clinical trials without further development.