image: Treatment schedule in an immunocompetent mouse model bearing a high burden of Burkitt’s lymphoma. While conventional CAR-T therapy alone resulted in no cures, adding five doses of a SUMOylation inhibitor led to long-term survival in 80% of the mice.
Credit: Kanazawa University
Burkitt's lymphoma is a rare and aggressive blood cancer characterized by a translocation of the MYC gene. It occurs most often in children and young adults. In recent years, CAR-T cell therapy—often referred to as a “living drug” and administered as a single dose—has been approved for certain types of blood cancer, offering hope for a cure even in severe cases. However, its effectiveness against Burkitt's lymphoma has been limited. Moreover, developing drugs that directly target MYC—the root cause of this cancer—has proven challenging for decades.
Recently, a study led by Dr. Hiroshi Kotani, Assistant Professor at Kanazawa University in collaboration with a scientist at Roswell Park Comprehensive Cancer Center in Buffalo, NY, USA, revealed that a SUMOylation inhibitor can suppress MYC activity (1). Building on this finding, the research team investigated whether combining CAR-T therapy with the SUMOylation inhibitor TAK-981 could improve outcomes for Burkitt's lymphoma.
The team first confirmed that the SUMOylation inhibitor effectively slowed the growth of Burkitt's lymphoma cells and altered their signaling pathways. They then examined the inhibitor's effect on CAR-T cells and discovered a dual role: while it initially activated the CAR-T cells in a way that could hinder long-term effectiveness, it also triggered a built-in "safety brake" mechanism. These insights suggested that using only a limited dose of the inhibitor could maximize the benefits of CAR-T therapy as a durable, living treatment.
In mouse models of Burkitt's lymphoma, the researchers tested a combination of CAR-T therapy with a single dose of the SUMOylation inhibitor. This approach extended the animals' survival, but did not cure the disease. However, when CAR-T therapy was paired with a short course of five inhibitor doses, an impressive 80% of the mice were cured and remained cancer-free long-term. These results demonstrate that carefully timed, limited use of a SUMOylation inhibitor can significantly enhance the curative power of CAR-T therapy against Burkitt's lymphoma.
"Relapsed or refractory Burkitt’s lymphoma has an extremely poor prognosis, and the development of new treatment strategies is urgently needed. These findings offer a strong rationale for developing a new, potentially curative treatment strategy for Burkitt's lymphoma," said Dr. Kotani. “We hope this study will be recognized as an example of research in cancer therapeutics that aims to eradicate cancer and improve treatment outcomes through a multifaceted approach."
[Reference]
1) Kotani H, et al. Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage. J Biomed Sci. 2024;31(1):68. doi: 10.1186/s12929-024-01060-3.
[Funding]
This work was supported by JSPS KAKENHI grant number JP23744746 and the Scholarship Donation Program by Daiichi-Sankyo.
[About Kanazawa University]
— Contributing to Society through “Future Oriented Intelligence”, Built on an “All Kanazawa University” Approach.
Kanazawa University (KU), founded in 1862, is a research university dedicated to education, while opening up its doors to both local and global society. Guided by our vision, “Kokorozashi,” we contribute to society through “Future-oriented Intelligence,” addressing current challenges and anticipating future ones from both local and global perspectives.
KU includes 4 colleges, 20 schools, 7 graduate schools, a hospital, and specialized research centers such as the Cancer Research Institute, a leading hub for research on cancer metastasis and drug development. Over 1,000 researchers drive innovation and international collaboration across diverse fields.
KU is advancing research through WPI (World Premier International Research Center Initiative) and J-PEAKS (Program for Forming Japan’s Peak Research Universities), accelerating interdisciplinary and international collaborations and innovations.
Learn more here: https://www.kanazawa-u.ac.jp/
[About Kanazawa University Cancer Research Institute (KU-CRI)]
The Kanazawa University Cancer Research Institute (KU-CRI), founded in 1967 as the only institute solely dedicated to cancer research among the Research Institutes and Centers of Japan National Universities, has conducted comprehensive studies ranging from basic research to clinical applications in the field of oncology.
Learn more here: https://ganken.cri.kanazawa-u.ac.jp/eng/
Journal
Signal Transduction and Targeted Therapy
Article Title
Limited SUMOylation inhibitor administration enhances eradication of Burkitt’s lymphoma with CD19 CAR-T therapy
Article Publication Date
3-Oct-2025