Protein May Help Cancer Cells Evade CAR T-Cell Therapy
New Drug Shows Promise in boosting CAR T-Cell Therapy for Blood Cancers
Researchers at City of Hope have identified a potential game-changer in the fight against blood cancers, paving the way for more effective CAR T-cell therapy.
(City of Hope, CA) – December 18, 2024 – A groundbreaking study published in Cell reveals a new target for enhancing the effectiveness of CAR T-cell therapy, a revolutionary treatment for certain types of leukemia and lymphoma. the research, led by scientists at the Beckman Research Institute of City of Hope, focuses on a protein called YTHDF2, which appears too play a crucial role in helping cancer cells evade the immune system.
CAR T-cell therapy works by engineering a patient’s own immune cells to recognize and destroy cancer cells. However, a significant challenge has been the phenomenon of “antigen escape,” where cancer cells reduce or lose the specific markers that CAR T-cells target, rendering the treatment less effective.
“One of the biggest hurdles in treating blood cancers is antigen escape,” explains Dr. Jianjun Chen, co-senior study author and the Simms/mann Family Foundation Chair in Systems Biology at City of Hope.”Cancer cells can essentially become invisible to the immune system by shedding these markers, making CAR T-cell therapy less accomplished.”
The study found that YTHDF2 plays a key role in this process. This protein helps cancer cells produce a stable energy source, fueling their growth and spread. Additionally, YTHDF2 helps cancer cells hide from the immune system by reducing the presence of these crucial antigen biomarkers.
“we discovered that YTHDF2 acts like a switch, turning on genes that allow cancer cells to thrive and evade detection,” says Dr. Zen-Hua chen, lead study author and a staff scientist in Systems Biology at City of Hope.
To combat this,the researchers developed a novel compound called CCI-38,designed to specifically target and suppress YTHDF2. In laboratory studies, CCI-38 substantially reduced the growth of aggressive blood cancers and enhanced the effectiveness of CAR T-cell therapy.
“Our findings suggest that targeting YTHDF2 with CCI-38 could significantly improve the success rate of CAR T-cell therapy for blood cancers,” says Dr. Jianjun Chen.
The researchers have filed a patent application for this promising discovery, which could have implications for treating other cancer types and autoimmune diseases. The next steps involve refining CCI-38’s safety and effectiveness, exploring new methods to eliminate YTHDF2 from cancer cells, and ultimately launching clinical trials to test its efficacy in humans.
This breakthrough research offers renewed hope for patients battling blood cancers, perhaps leading to more personalized and effective treatment options in the future.
Hope on the Horizon: New Drug Could Supercharge CAR T-Cell Therapy for Blood Cancers
Blood cancer patients may soon have a powerful new ally in their fight against the disease. City of Hope researchers have identified a potential game-changer that could considerably improve the effectiveness of CAR T-cell therapy,a revolutionary treatment that utilizes the body’s own immune system to destroy cancer cells.
Published in the prestigious journal Cell, the groundbreaking study highlights the role of a protein called YTHDF2, which allows cancer cells to evade the immune system. CAR T-cell therapy works by engineering a patient’s immune cells to target specific markers on cancer cells. However, cancer cells can often “escape” detection by minimizing or eliminating these markers, rendering CAR T-cell therapy less effective.
“Cancer cells can essentially become invisible to the immune system by shedding these markers,” explains Dr. Jianjun Chen, co-senior study author adn the Simms/mann Family Foundation Chair in Systems Biology at City of Hope. “This phenomenon, called antigen escape, is one of the biggest hurdles in treating blood cancers.”
The study found that YTHDF2 is a key player in this escape process. It helps cancer cells produce a stable energy source, allowing them to grow and spread, while simultaneously reducing the presence of those crucial antigen biomarkers.
“We discovered that YTHDF2 acts like a switch, turning on genes that allow cancer cells to thrive and evade detection,” says lead study author Dr. Zen-Hua Chen, a staff scientist in Systems Biology at City of Hope.
To counter this, researchers developed a novel compound called CCI-38 specifically designed to suppress YTHDF2. In laboratory studies, CCI-38 substantially inhibited the growth of aggressive blood cancers and significantly enhanced the effectiveness of CAR T-cell therapy.
“Our findings suggest that targeting YTHDF2 with CCI-38 could significantly improve the success rate of CAR T-cell therapy for blood cancers,” says dr. Jianjun Chen.
This finding has led to the filing of a patent application and holds promising implications for treating other cancers and autoimmune diseases. Future steps include refining CCI-38’s safety and effectiveness, exploring new methods to eliminate YTHDF2 from cancer cells, and ultimately launching clinical trials.
This landmark research offers renewed hope for patients battling blood cancers and potentially paves the way for more personalized and effective treatment options in the future.