UCLA Scientists Turn Cord Blood Into Cancer-Fighting T Cells

T cell receptor therapy, or TCR therapy, genetically modifies immune cells called T cells to recognize and attack cancer with high precision. Unlike chimeric antigen receptor (CAR) T-cell therapy, which recognizes proteins on a cancer cell's outside, TCR therapy can also detect protein fragments from inside a cancer cell that are carried to its surface -- a reach that matters for solid tumors.

TCR therapy's biggest obstacle is cost and speed: current approaches need a personalized treatment made from each patient's own T cells, taking weeks and costing well into six figures. Ready-made treatments from healthy donors' T cells can also trigger graft-versus-host disease (GVHD), where transplanted immune cells attack the patient's healthy tissue.

Researchers at the University of California, Los Angeles (UCLA) say they have addressed both problems. In a study in the journal Cell Reports Medicine, they describe making cancer-targeting AlloESO-T cells from blood stem cells in donated cord blood, not mature donor T cells, engineered to recognize NY-ESO-1, a protein common in solid tumors. "This platform brings us closer to a future where the product is already made, frozen and ready to go as soon as the patient needs," said co-senior author Lili Yang, a UCLA professor.

Because the receptor is added at this early stem cell stage, the resulting cells skip the random natural T cell receptors found on donor T cells, avoiding the extra gene editing conventional donor-cell therapies require. Co-first author Yichen (John) Zhu, a UCLA graduate student, said essentially all the resulting cells carry the same receptor and target the same tumor.

Solid tumors are diverse, and some cancer cells stop displaying that target marker, called antigen escape. AlloESO-T cells also carry natural killer (NK) cell receptors that sense stress signals on tumor cells, a backup confirmed in lab tests on human melanoma, ovarian and prostate cancer cells. In mouse models, a single dose controlled ovarian tumor growth and extended survival without dangerous side effects, and slowed melanoma growth, while cells made from mature donor T cells gave only partial tumor control and caused GVHD.