Engineered T cells recruit a second wave in culture
An engineered signal-receptor pair directed T cells to signal-producing tumors in mice and supported self-amplifying recruitment in cell culture, with therapeutic benefit still unestablished.
Engineered T cells recruited a second wave to a tumor target
In cell culture, the first T cells to encounter a tumor target began releasing a signaling protein. It recruited a second, much larger wave of T cells. When those cells encountered the target, they also released the signal, increasing recruitment.
Wendell Lim’s group at the University of California, San Francisco is programming the movement of T cells, a type of immune cell. In a 2014 study, the researchers directed modified T cells toward drug-containing beads implanted in mice. In the new work, both the signal and its matching receptor are genetically encoded in cells.
The authors modified the chemokine CCL20 and its receptor CCR6. Chemokines act as signals: immune cells carrying a matching receptor move toward higher concentrations. Natural chemokines can also recruit cells that suppress the immune response, so the authors sought to make the engineered pair selective. None of the 44 natural chemokines tested appreciably activated the modified receptors. Human blood cells that migrated toward natural CCL20 did not migrate toward the modified signal. These results show little cross-talk with the tested part of the natural signaling network; they do not establish complete isolation under every condition.
In culture, signal production was controlled by synNotch, an engineered receptor that switches on a chosen gene when it encounters a specified protein. The first T cells approached a small ball of tumor cells in response to the natural chemokine CXCL12. Encountering the protein CD19 on those cells triggered production of the engineered signal. Without CD19, there was no second wave.
In immunodeficient mice, T cells preferentially accumulated in a tumor made from human lung cancer cells that produced the engineered signal. Self-amplifying recruitment has so far been shown only in culture. The supplied material reports no results on tumor destruction or evidence of safety and therapeutic efficacy in people.
The group posted the work on October 14, 2026 as a preprint, a manuscript that has yet to undergo peer review. Assessing its therapeutic potential will require testing whether cells recruit further waves inside the body and whether that improves tumor treatment.
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Sources
[1] biorxiv.org
[2] doi.org
[3] doi.org
[4] limlab.ucsf.edu
This item extends a research line at the University of California, San Francisco from externally supplied guidance signals to immune cells that can produce their own recruitment signal, making the university’s Eternal Search page a relevant entry point.