The Yale laboratory of Sidi Chen, assistant professor of genetics in the Systems Biology Institute and Yale Cancer Center, has developed advanced gene-editing and screening technology to find new targets for cancer immunotherapy.
In a new study published in Nature Biotechnology, Chen and colleagues report that using T cells containing modifications of those gene targets reduced tumors in a mouse model of glioblastoma, a brain cancer that is especially difficult to treat.
Multi-colored markers of the immune system are captured in glioblastoma tumors.
The brain has a very limited immune system activity and therefore is not a particularly promising organ for immunotherapy, note the researchers. Chen’s lab developed a sophisticated viral vector with an embedded transposon, or jumping gene, that facilitates the genetic screening capabilities of T cells.
Genomic screens of T cells uncovered one target, PDIA3, that when inhibited in T cells suppress glioblastoma tumor growth in mice. They also showed that knocking out PDIA3 in a specific type of T cells can enhance their cancer-killing properties in human glioblastoma cells.
Chen said similar techniques could be employed on different immune cells and other types of cancers that so far have been impervious to immunotherapy.