Scientists 'supercharge' cancer-fighting T cells

Date:
March 10, 2022
Source:
Yale University
Summary:
Scientists have identified a way to 'supercharge' tumor-attacking
T cells, a finding that may not only improve the effectiveness
of a promising type of cell-based cancer immunotherapy but also
expand the number of cancers it can treat.



FULL STORY ==========================================================================
Yale scientists have identified a way to "supercharge" tumor-attacking
T cells, a finding that may not only improve the effectiveness of a
promising type of cell-based cancer immunotherapy but also expand the
number of cancers it can treat.


========================================================================== Their findings are published March 10 in the journal Cell Metabolism.

The discovery can advance CAR-T cell therapy, which harnesses the immune response of T cells to cancers by introducing tumor-detecting molecules
into the cells. In the last decade, the U.S. Food and Drug Administration
has approved six CAR-T cell therapies to treat B cell lymphomas and
multiple myeloma. But despite early successes, the effectiveness of the treatment tends to diminish over time, which has launched a search for
ways to boost function of T cells.

Also, there are currently no approved CAR-T cell therapies to treat
solid tumors.

For the new study, researchers in the lab of Sidi Chen, associate
professor of genetics at Yale and senior author of the paper, devised an ingenious way to efficiently scan the genome of CD8 T cells for specific
genes that might enhance the cells' ability to attack cancer cells.

"We developed a new kind of genome-wide gain of function screen to find
a molecular enzyme that acts like a foot on a gas pedal to increase
metabolic activity in T cells," Chen said.

They found high levels of activity in several genes, including PRODH2, a
gene involved in cell metabolism, stimulate increased CAR-T cell activity
in mouse models used to study three different types of cancers, including solid-tumor breast cancer. The findings show it is possible to produce hyper-metabolic CAR- T cells that outperform existing cell therapies, researchers say.

Using these systems and findings, future studies can test the newly
identified types of metabolically enhanced CAR-Ts in clinical settings,
to identify other T cell super-chargers, and to extend cell-based
immunotherapy to different cancer types, especially solid tumors,
Chen said.

Chen is affiliated with the Yale Cancer Center, the Yale Stem Cell Center,
the Yale Center for Biomedical Data Science, and the Systems Biology
Institute and Center for Cancer Systems Biology at Yale's West Campus.

Yale's Lupeng Ye, Jonathan Park, Lei Peng, and Quanjun Yang are co-first authors of the paper.

The research was primarily funded by the National Institutes of Health
and the U.S. Department of Defense.


========================================================================== Story Source: Materials provided by Yale_University. Original written
by Bill Hathaway. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Lupeng Ye, Jonathan J. Park, Lei Peng, Quanjun Yang, Ryan D. Chow,
Matthew B. Dong, Stanley Z. Lam, Jianjian Guo, Erting Tang,
Yueqi Zhang, Guangchuan Wang, Xiaoyun Dai, Yaying Du, Hyunu
R. Kim, Hanbing Cao, Youssef Errami, Paul Clark, Alexey Bersenev,
Ruth R. Montgomery, Sidi Chen. A genome-scale gain-of-function
CRISPR screen in CD8 T cells identifies proline metabolism as
a means to enhance CAR-T therapy. Cell Metabolism, 2022; DOI:
10.1016/j.cmet.2022.02.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220310170827.htm

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