The study with Nix and Gourisankar as lead authors appeared in Cell on July 20, 2026, according to Stanford Medicine, with Crabtree, Gray, Hinshaw, and Green as co-senior authors.
According to Stanford Medicine, diffuse large B-cell lymphoma is often driven by BCL6.
In healthy immune cells, BCL6 temporarily suppresses genes that would trigger cell death according to Stanford Medicine, allowing these cells to proliferate during an immune response; in BCL6-driven lymphomas, this switch remains permanently on. Researchers used a process called chemically induced proximity, in which molecules that normally interact rarely are brought together through chemical bonds. According to Nix, one side of TCIP3 binds to BCL6, the other to p300 or CBP; their acetyl marks block BCL6's suppression. Nix explained that the approach removes suppression while simultaneously actively driving cell death gene expression, explaining the compound's high efficacy.
The Mouse Study and Its Limits — Mice were treated with TCIP3 twice daily according to Stanford Medicine.
The treated animals showed no obvious signs of toxicity according to Stanford Medicine and no sharp spike in inflammatory signals in blood, even though TCIP3 simultaneously dissolved germinal centers of immune cells, the cell type dysregulated in lymphomas.
In Cell Tests More Effective and Gentler Than p300/CBP Comparators
In cell culture experiments with SUDHL5 lymphoma cells, TCIP3 was 238 times more effective than A-485 and 12 times more effective than dCBP-1, both of which also target p300/CBP. At the same time, TCIP3 damaged B and T cells from tonsil tissue from two donors and primary human fibroblasts substantially less than SUDHL5 cells and was gentler than the comparison drugs. On cell lines with low BCL6 levels, TCIP3 was as effective as the combination of GNE-781 and BI-3812; the advantage appeared mainly at high BCL6 levels. These comparison values come from a study version not yet peer-reviewed at the time of publication; the source page now refers to a peer-reviewed version in Cell.
What Broader Application Still Needs
According to Stanford Medicine on August 19, 2026, researchers were already searching for other cancer-driving proteins for the same approach and suspected that molecules like TCIP3 could eventually work against autoimmune diseases like rheumatoid arthritis and myasthenia gravis, since germinal center cells also drive these diseases. According to Stanford Medicine on August 19, 2026, Crabtree and Gray were co-founders and advisors to Shenandoah Therapeutics, which at that time held a license for the TCIP technology from Stanford.