Studies Test CAR T-Cell Therapies Designed to Overcome Key Limitations
February 8, 2023, by Sharon Reynolds
Over the last decade, the idea of engineering a personalized immune response to cancer has gone from theory to reality. CAR T-cell therapies, which are made using patients’ own immune cells, have been transformative for some types of aggressive leukemias and other blood cancers. In some cases, they’ve even cured people whose cancer has come back after many other treatments.
But CAR T cells don’t yet lead to long-term survival for most people. And making the leap from treating cancers of the blood to treating solid tumors, like pancreatic, lung, or colorectal cancer, has proven daunting.
Immune cells face a range of challenges when attacking solid tumors. These include an environment full of molecules that can block or disarm immune cells, competition from other cells for scarce nutrients, and over time, a diminished ability to kill other cells, a phenomenon often referred to as exhaustion.
Two research teams have now developed novel ways for overcoming these challenges. One team created CAR T cells that can produce their own fuel upon contact with a tumor. The other engineered CAR T cells in which certain cellular functions can be turned on and off at specific times in response to the administration of certain drugs.
In mice, both types of souped-up CAR T cells shrank solid tumors, including pancreatic cancer and melanoma, much more effectively than standard CAR T cells.
What’s especially exciting, explained Grégoire Altan-Bonnet, Ph.D., of NCI's Laboratory of Integrative Cancer Immunology, who co-wrote an editorial on the studies, is the potential for combining these two techniques into a single therapy, which could be adjusted in individual people over time.
Such an application would require years more work, but “now that we have these tools, it’s going to open up a lot of possibilities,” Dr. Altan-Bonnet said.
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