Cancer researchers just found a brand new solution to tackle tumors.
CAR T cell therapy revolutionized blood cancer treatment by supercharging a patient’s own immune cells to seek out cancers. However the approach has struggled in solid cancers. These are a few of our top killers—breast, lung, prostate. Roughly two million Americans are expected to be diagnosed with cancer in 2026, and over 600,000 will likely succumb to the disease.
Unlike blood cancers, solid tumors rarely share a single, universal goal for CAR T cells. Even cells throughout the same tumor are a mishmash. Some have little or none of a goal protein, allowing them to evade the engineered immune cells, survive treatment, and fuel relapse.
“Goal discovery stays a substantial challenge in the event and translation of
CAR T cell therapies for solid tumors,” wrote Christopher Mount and Marcela Maus on the Massachusetts General Brigham Cancer Institute.
Now, two independent teams have converged on the identical promising goal: A cell-surface protein called GPNMB. In one study, CAR T cells engineered to acknowledge GPNMB rapidly destroyed glioblastoma—a lethal brain cancer—in tissues taken from patients and shrank tumors in mice.
A second team used the same strategy against an aggressive soft tissue cancer to fight tumors in organoids and mice. In an early clinical trial involving a single participant, one infusion stabilized the disease for 3 months without serious unintended effects.
CAR T designers are sometimes wary of broadly shared targets because they’ll trigger dangerous attacks on healthy tissue. But GPNMB is an odd duck. Along with cancer cells, it also sits on immune cells that spur cancer growth or suppress the body’s innate ability to eliminate tumors.
“Our approach attacks each the tumor and the environment that permits it to thrive,” said Sheila Singh at McMaster, who led the glioblastoma study, in a press release. “We’re going beyond targeting the cancer alone and eliminating the immune cells that help shield it from treatment.”
Cancer Fortress
Solid cancers have loads of tricks to outsmart CAR T cells.
Researchers make these supercharged immune cells by extracting a patient’s own T cells and genetically engineering them to provide protein “claws” that latch onto a particular cancer goal. After infusing the cells back into the body, they seek and destroy tumor cells. CAR T has transformed treatment for several blood cancers and is showing promise in autoimmune diseases and excessive heart and kidney scarring. To simplify the procedure, researchers are also exploring ways to directly transform T cells contained in the body with gene therapy.
Solid cancers, nevertheless, are far tougher opponents. Unlike blood cancers, that are heavily coated with a shared goal called an antigen, solid tumors are molecular patchworks. Cells throughout the same tumor can display different targets—or none in any respect—allowing some to evade a CAR T attack and trigger relapse. A lot of these targets also appear on healthy tissues, raising the chance of dangerous unintended effects. After which there’s the tumor microenvironment: A toxic, glue-like “fortress” that hijacks immune cells and uses them to battle incoming CAR T cells.
These barriers aren’t impenetrable. Previous work enlisted bacteria to assist CAR T cells burrow into tumors. Other efforts engineered ultra-sensitive CAR T cells able to detecting tiny amounts of a cancer goal shared across multiple solid tumors.
“Recent reports of activity in several clinical trials reinforce optimism that these efforts may lead to true clinical profit,” wrote Mount and Maus, who weren’t involved in either study.
But these strategies require additional engineering steps, increasing complexity and value. And most still leave one major roadblock intact: The tumor’s immune defenses.
One-Two Punch
Within the glioblastoma study, the team at McMaster University scoured donated tumors for proteins that distinguished essentially the most aggressive cancer cells. They found one standout: GPNMB. One other test of each protein dotting the cell surface confirmed it as a promising goal. The protein is clear across a cancer cell’s membrane, making it readily accessible to CAR T cells.
In lab tests, CAR T cells engineered against GPNMB performed well, nearly eliminating tumors grown from patient samples and lengthening survival in mice.
The goal turned out to be much more helpful than expected. The team soon realized that GPNMB also marked the immune cells that suppress anti-cancer drugs. CAR T cells attacked each fronts concurrently, weakening the tumor’s immune shield and killing the cancer itself.
“Most approaches have focused on killing cancer cells alone,” said study creator Shan Grewal. “Our work suggests we can also must dismantle the immune support system that helps the tumor survive.”
The second team focused on alveolar soft-part sarcoma, a rare soft-tissue cancer that usually spreads to the lungs, brain, and bones before it’s diagnosed. Treatment often comes too late.
The disease is driven by a sort of “fusion” gene created when pieces of genetic material are unintentionally stitched together. These genes are extremely tough to focus on directly. As an alternative, the team screened all surface proteins on the cancer cells and again landed on GPNMB as a top candidate for intervention. The protein’s levels closely tracked the activity of the fusion gene.
CAR T cells targeting GPNMB cleared tumors and prevented metastasis in mice. But because an earlier antibody drug against the protein caused severe skin toxicity in patients, the team also tested their CAR T cells in mice carrying small human skin grafts. Although inflammation initially flared, there have been no signs of ongoing skin damage.
Encouraged, the team treated a patient with relapsed, metastasized alveolar soft-part sarcoma. After a single infusion, the engineered cells rapidly divided within the bloodstream and remained detectable for roughly a month. The treatment didn’t trigger skin rashes or more dangerous unintended effects, like cytokine release syndrome where the body mounts a hyperactive immune defense that harms healthy organs.
The treatment’s advantages outlasted the engineered cells themselves. For roughly three months, imaging tests found fewer of the small, round spots on the patient’s lungs that usually signal metastatic cancer, suggesting the disease had stabilized.
A final evaluation identified one other roadblock: Clusters of cells that suppress the immune system and will blunt the advantages. Adding drugs to dam these immune molecules boosted tumor killing in mice. Because the identical form of gene fusion drives other cancers, including kidney, the CAR T cells could have reach beyond this specific sort of sarcoma.
Together, the studies underscore that the most effective CAR T targets might extend beyond cancer cells to show and attack cancer’s immune cell supporters too. Finding a viable goal is a fragile balancing act. Chosen well, and CAR T cells could tackle multiple drivers for cancer growth. Select poorly, and healthy tissues could get hurt within the crossfire.
Even so, “these two studies indicate that GPNMB represents an actionable goal for CAR T cell therapies in several solid tumors,” wrote Mount and Maus.