Brussels - California: Europe and the Arabs
After their success in combating blood cancers, CAR T cells are preparing to take on a more difficult battle: combating solid tumors, which represent the vast majority of cancer cases and pose the greatest challenge to modern immunotherapies.
Nature Biomedical Engineering published the results of a recent study conducted by researchers from the USC Norris Comprehensive Cancer Center in the United States, in collaboration with City of Hope. The study reveals an innovative design for T cells that makes them more capable of combating cancers that account for approximately 90% of cases worldwide, including prostate, breast, lung, and ovarian cancers. Under the title "A New Design to Boost the Immune Attack," the European news website in Brussels, "Euronews," wrote: The design relies on combining two proteins within T cells: the cytokine interleukin 12 (IL-12), known for its ability to enhance immune activity, with the PD-L1 inhibitor, one of the immune checkpoint inhibitors used by tumors to stop T-cell attacks. When tested in mouse models of ovarian and prostate cancer, the modified cells launched a localized attack that effectively shrank tumors without causing widespread collateral damage to the rest of the body.
"With this new design of CAR T cells, we can make the treatment safer and more effective, even against resistant tumors," said lead author Saul Priceman, associate professor at the Keck School of Medicine at USC and founding director of the Keck/Norris Center for Cellular Immunotherapy in Cancer.
The primary challenge facing CAR T therapy has always been the hostile environment within solid tumors, which hinders T cells from functioning and weakens their ability to attack.
Although IL-12 has long been a promising tool for immune regeneration, its direct administration causes serious toxicity. The new solution is to precisely deliver IL-12 to the tumor by attaching it to a PD-L1 inhibitor, so that it is released into the area where tumors naturally raise levels of this protein when confronted with immune cells.
In this way, the researchers ensured that IL-12 delivered directly to the tumor while neutralizing collateral damage, creating a more conducive environment for immune attack. The team's tests in mice showed that the approach not only expanded the ability of T cells to penetrate tumors but also limited toxicity in healthy tissue, making its transfer to patients a feasible goal.
A Step Toward Clinical Trials
John Murad, assistant professor in the Department of Medicine at USC and the study's first author, summarized the vision, saying, "We believe this new strategy will significantly advance current CAR T therapies and could be applied to several types of cancer."
The research team hopes to move the technology to clinical trials within one to two years. Beyond CAR T cells alone, the approach may contribute to improving the engineering of other types of "fighting" immune cells, such as tumor-infiltrating lymphocytes and T-cell receptor-positive T cells.