Two independent studies published this week in Cell and Nature Immunology tackle the same problem from opposite angles: how to make cancer immunotherapy more effective and more durable. The first, from the University of Southern California, addresses the challenge of supply by finding a way to grow large numbers of engineered immune cells indefinitely. The second, from Cold Spring Harbor Laboratory, focuses on performance, showing that activating a specific metabolic protein can turn immune cells into stronger tumor killers.
The USC team worked with immature immune cells called granulocyte-monocyte progenitors, or GMPs, which normally develop into macrophages and other defender cells. Under carefully controlled lab conditions, these progenitors could multiply extensively while retaining their ability to mature into functional immune cells. When genetically modified and introduced into mice, the cells established themselves in bone marrow, produced new immune cells, and slowed tumor growth in both blood cancers and solid tumors. The findings challenge the traditional view that long-term self-renewal in the blood system belongs mainly to hematopoietic stem cells.
The Cold Spring Harbor team, led by Semir Beyaz, took a different approach. They activated a protein called PPARD, a transcription factor involved in fat metabolism, inside engineered CAR T cells. In experimental models of colorectal, breast, and ovarian cancer, as well as melanoma, the activated cells burned more fat and became more effective at attacking tumors. Beyaz suggests the approach could extend beyond cancer, possibly helping treat chronic conditions like endometriosis. While both studies are early-stage and not yet proven in humans, together they suggest that improving both the quantity and the metabolic fitness of engineered immune cells could be key to making next-generation immunotherapies work for more patients. The studies agree on the goal of strengthening cellular immunotherapy, but they target different bottlenecks: one in production, the other in function.