New Hope for Small Cell Lung Cancer: Advances in CAR-T Cell Therapy
This type of cancer grows quickly and is difficult to treat. One reason for this is that tumor cells can evade the immune system. Typically, immune cells recognize cancer cells via specific surface structures. In SCLC, however, these structures are often reduced, making it harder to detect the cancer cells.
This is where CAR-T cell therapy comes into play. In this process, immune cells are modified in a laboratory setting so they can recognize and attack cancer cells, even when they are hiding from the immune system. Current research focuses on a target structure called B7-H3 that is found on tumor cells. Additionally, researchers have modified the immune cells to activate a factor called c-JUN. This enables the cells to remain functional longer and fight tumor cells more effectively.
The study “c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors” - published in Cell Reports Medicine - shows that these enhanced CAR-T cells react particularly strongly to tumor cells. They release more signaling molecules that support the immune response and lose their effectiveness more slowly than previous approaches. This is an important advancement because CAR-T cell therapies for solid tumors have often failed in the past due to immune cell exhaustion.
Another important step is the production of the therapy. Researchers demonstrated that CAR-T cells can be produced without using viruses. This method is considered safer and more cost-effective, and it can be implemented on a larger scale. Furthermore, production under strict clinical quality standards has been demonstrated, which is a prerequisite for its future use in patients.
Building on these results, the “FOCuS project” was launched. The T Cell and Genome Engineering Lab at the University Hospital of Cologne (under the leadership of Dr. Hyatt Balke-Want), the Lung Cancer Group Cologne (led by Dr. Felix John, a resident at Department I for Internal Medicine at the University Hospital of Cologne), the Fraunhofer Institute for Cell Therapy and Immunology and the Cologne based company LIQOMICS GmbH (Dr. Sven Borchmann) are collaborating to further develop the non-viral CAR-T cell platform and advance it toward clinical application. The state of North Rhine-Westphalia is funding the project with over two million euros through the Gesünder.IN.NRW innovation competition, using European Union funds. The goal is to establish the technology in a GMP environment and, eventually, use it at the University Hospital of Cologne for initial clinical trials.
First author of the study Dr. Hyatt Balke-Want, who is member of the Career Advancment Program at the Center for Molecular Medicine COlogne (CMMC), says: “We are, of course, very pleased that the clinical development of our non-viral production method for anti-B7-H3 CAR T cells is now being funded by the state of North Rhine-Westphalia, allowing us to continue seamlessly and potentially treat our first patients in the coming years.” He adds: “Thanks to our preliminary work, we now have a clear translational pathway. Furthermore, the combined Type I and II cytokine expression mediated by c-JUN represents a very exciting finding that we will continue to investigate in order to improve the effectiveness of CAR T cells.”
Original Publication
https://www.sciencedirect.com/science/article/pii/S2666379125006226?via%3Dihub
Hyatt Balke-Want*, Vimal Keerthi, Maria Del Carmen Arenas, Yiyun Chen, Meena Malipatlolla, Dorota D. Klysz, Peng Xu, Katie Ho, Kyle Asano, David Stahl, Jing Huang, Aidan Retherford, Sunny Patel, Carley Fowler, Lukas Maas, Nikolaos Gkitsas-Long, Qiaoshi Jiang, Xikun Liu, Roland Ullrich, Julie George, Sabine Heitzeneder, Ramya Tunuguntla, Julien Sage, Elena Sotillo, Crystal L. Mackall*, Steven A. Feldman*, “c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors”, Cell Rep Med, 2026 Jan 20;7(1):102549. doi: 10.1016/j.xcrm.2025.102549
Authors with CMMC affiliation indicated in bold and leading / first authors are indicated with a star (*) .
This message has been modified by the CMMC (K. Heber & D. Grosskopf-Kroiher) and is based on the text by the press and communications teams of the University Hospoital Cologne (original German version here).