Researchers at UCLA have developed a new “off-the-shelf” cell therapy that transforms cord blood stem cells into T cells that can attack solid tumours, according to a study published in Cell Reports Medicine. In mouse models, a single dose of these engineered cells — called AlloESO-T — controlled tumour growth and extended survival, offering a potentially faster, cheaper, and safer alternative to existing cancer treatments.
The therapy uses a technique known as TCR (T-cell receptor) therapy, which differs from the more familiar CAR T-cell approach by targeting protein fragments found inside cancer cells rather than only on their surface. This is especially useful for solid tumours, where many cancer-driving changes occur internally.
Rather than starting with mature donor T cells, the UCLA team engineered immature cord blood stem cells to carry a receptor that targets NY-ESO-1, a protein common in many solid tumours. Because the cells are modified at such an early developmental stage, nearly all resulting T cells uniformly target the same cancer marker, and the process avoids the random receptor mix found in typical donor T cells — reducing the risk of the cells attacking healthy tissue.
To counter “antigen escape”, where tumours stop displaying their identifying markers, the cells were also equipped with natural killer cell receptors that detect general tumour stress signals, giving them a backup targeting mechanism.
In mice with ovarian cancer and melanoma, AlloESO-T cells multiplied roughly 100-fold after a single infusion, concentrated in tumours, and avoided the organ toxicity and graft-versus-host disease seen with conventional donor-derived T-cell therapies.
Manufacturing is a key advantage: researchers estimate that a small supply of cord blood stem cells could yield trillions of therapeutic cells — enough for thousands of doses — within about six weeks, at an estimated cost of $5,000 per dose, far below today’s six-figure personalised treatments.
The therapy has so far only been tested in mice and has not been evaluated in human clinical trials or approved by the FDA. Researchers plan to scale up manufacturing with UCLA Health’s Center for Advanced Biotherapies as a step toward future clinical testing.
(Cell Reports Medicine)