This study explores a new type of cancer immunotherapy based on CAR-NK cells—natural killer cells that are genetically engineered to better recognize and destroy cancer cells. In this case, the therapy targets HER2, a protein commonly found on certain cancer cells, such as some breast cancers.
One of the main challenges in treating solid tumors is that they can “hide” from the immune system. They are often surrounded by a dense, fibrous environment that physically blocks immune cells from entering the tumor. This makes many modern immunotherapies less effective.
To overcome this, the researchers enhanced CAR-NK cells by adding two signaling components, 2B4 and 4-1BB, which act like internal “boosters.” This combination made the cells more active and longer-lasting. In laboratory models, these engineered cells were able to penetrate deep into tumors and kill cancer cells throughout the entire structure, not just on the surface.
Animal experiments showed similarly promising results: the modified CAR-NK cells significantly reduced tumor size, improved survival, and in some cases led to long-term remission.
Overall, the study suggests that making immune cells stronger and better equipped can help them overcome the defenses of solid tumors, offering a promising new direction for treating difficult, therapy-resistant cancers.
The article was published in the international journal *Cancer Letters* on April 25, 2026. DOI
Gergely B, Vereb M, Rebenku I, Szöőr Á, Vereb G. Breaking the barrier: Synergistic 2B4.4-1BB signaling potentiates HER2-CAR NK cells to penetrate and destroy ADCC-resistant tumors. Cancer Lett. 2026 Apr 25:218534. doi: 10.1016/j.canlet.2026.218534. Epub ahead of print. PMID: 42044866.