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Excellent overview of CAR-T...

The Immune System Fights Back
Reprogrammed T cells show promise at beating blood cancers, but other foes may be tougher to vanquish

http://cen.acs.org/articles/92/i40/Immune-System-Fights-Back.html

THE NEXT FIGHT
While companies sort out the nuances of bringing CARTs for blood cancer to market, they are also considering how to apply the technology to the wider world of solid tumors. It will be tricky. In CD19, researchers have as close to an ideal target as is possible in cancer. The receptor sits on both normal and cancerous B cells, but patients can live without healthy B cells as long as they are given immunoglobulin replacement therapy.

Similarly safe targets on solid tumors are less obvious. Moreover, solid tumors are harder to access. “When you’re dealing with a leukemia, you’ve got direct access to many of the cells circulating in the bloodstream,” says King’s College’s Maher, who is working on a CART for solid tumors. But solid tumors often have a complex microenvironment designed to deflect an immune attack, and many scientists question whether a CART for a solid tumor can elicit anywhere near the kind of response that it can in blood cancer.

Novartis’s Azam is sanguine about the prospects for moving CARTs into solid tumors, noting that the company even sees the technology being used one day in other disease areas, such as immunology. “There is clearly a very solid scientific rationale and basis for developing these in solid tumor types,” he says.

Novartis and Penn scientists are actively looking at diseases, such as pancreatic cancer, where few or no treatment options exist. Referring to solid tumors, Azam says Novartis is “definitely entering into clinical studies in a small-scale setting in the very near future.”

Beyond pursuit of other tumor types, researchers expect the coming years will bring new knowledge about how to pair CARTs with other treatments, particularly checkpoint inhibitors. “The cancer field really is built on combination therapy,” says David D. Chang, Kite’s chief medical officer. “There are a lot of discussions ongoing about combining CART therapy with other immunotherapy. I would say that the scientific rationale is strong and such a combination therapy is worth pursuing.”

Despite the many kinks to be worked out on how to optimize CARTs, researchers are happy to be making real progress in empowering T cells to fight cancer. They are betting that the technology will offer results of the type only dreamed about in the oncology world.

“A lot of people have talked a lot about personalized therapies and personalized medicines, but very few have achieved something successful in this space,” Azam says. “We feel we’re tantalizingly close to doing that.”