Scientists at City of Hope have identified a protein, YTHDF2, that helps blood cancer cells evade CAR T cell therapy, a treatment that uses the immune system to attack tumors. They also developed a compound, CCI-38, which targets and suppresses YTHDF2, thereby reducing cancer growth and improving treatment outcomes. This discovery stems from research published in the journal •Cell•.
This breakthrough is crucial for advancing blood cancer treatment, particularly for patients who relapse after CAR T cell therapy or whose cancers develop resistance. Current CAR T therapies often face challenges due to “antigen escape,” where cancer cells reduce or lose the CD19 protein targeted by the therapy. This new research tackles this issue by targeting a different mechanism – YTHDF2 – which not only contributes to cancer growth and spread but also helps cancer cells hide from the immune system. Addressing this previously untargeted protein offers a new avenue for improving treatment effectiveness and potentially overcoming resistance mechanisms.
The research details how YTHDF2 promotes cancer cell growth by enabling stable energy production and by reducing the presence of antigens that trigger immune responses. The newly developed compound, CCI-38, effectively suppresses YTHDF2, suggesting a potential combination therapy approach with CAR T cell treatment. This could lead to fewer relapses, reduced need for follow-up treatments, and ultimately, improved long-term survival rates for blood cancer patients.
This discovery opens exciting possibilities for blood cancer treatment. Targeting YTHDF2 with CCI-38, potentially in combination with CAR T cell therapy, could significantly enhance treatment efficacy and overcome current limitations like antigen escape. Further research and clinical trials will be essential to validate these findings and optimize the use of CCI-38, paving the way for more effective and personalized therapies for blood cancers and potentially other cancers and autoimmune diseases.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
