Scientists at UCLA have developed an "off-the-shelf" cell-based immunotherapy that was able to track down and kill pancreatic cancer cells even after they had spread to other organs.
In a mouse study, the treatment slowed cancer growth, extended survival and remained effective even within the harsh environment of solid tumors.
"Even when the cancer tries to evade one attack pathway by changing its molecular signature, our therapy is hitting it from multiple other angles at the same time. The tumor simply can’t adapt fast enough," lead author Dr. Yanruide Li, a post-doctoral scholar at UCLA, said in a press release.
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To build the therapy, researchers took human stem cells and turned them into a special type of immune cell called an invariant natural killer T cell (or NKT cell).
Next, they genetically modified those cells by adding a CAR receptor (chimeric antigen receptor), which enables the cells to recognize and attack pancreatic cancer cells.
NKT cells are naturally compatible with any immune system, which means they can enter the body without causing dangerous reactions, according to the researchers. They can also be mass-produced using any donated blood stem cells.
"One donor could provide sufficient cells for thousands of treatments," potentially offering a more affordable and accessible approach, according to the press release.
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The team tested the therapy in several lab models. These included models where the cancer was placed directly into the pancreas and others designed to mimic how the disease spreads to other organs, like the liver and lungs.
The CAR-NKT cells were able to push their way into the tumor itself, rather than getting stuck on the outside like many immune treatments do, the researchers found.
Once they got inside the body, these engineered immune cells could spot cancer cells in several different ways and kill them using multiple built-in attack methods.
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Most importantly, they stayed active. Many immune cells that enter a solid tumor quickly become overwhelmed and shut down, but these engineered cells kept working instead of burning out, allowing them to continue fighting the cancer for a longer period.
The findings were published in the journal PNAS (Proceedings of the National Academy of Sciences).
"Developing a therapy that targets both the primary tumor and its metastases in pre-clinical studies — one that can be ready to use off-the-shelf — represents a fundamental shift in how we might treat this disease," said senior author Dr. Lili Yang, a professor of microbiology, immunology and molecular genetics at UCLA, in the same press release.
The researchers noted that one dose could cost around $5,000, far lower than personalized CAR-T treatments.
Pancreatic cancer is notoriously aggressive and difficult to treat, according to the researchers. Most patients aren’t diagnosed until the disease has already spread, and the tumor’s biology creates multiple physical and chemical barriers that weaken the impact of traditional treatments.
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Since the therapy targets a protein that is common in breast, ovarian and lung cancers, the same cell product could potentially treat multiple cancer types.
In separate studies, the team has already demonstrated the therapy’s effectiveness against triple-negative breast cancer and ovarian cancer.
Based on the early findings, the UCLA researchers are preparing to submit applications to the Food and Drug Administration to begin human trials.
"We’ve developed a therapy that’s potent, safe, scalable and affordable," Yang said in the release. "The next critical step is proving it can deliver the same results in patients we’ve seen in our preclinical work."
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All testing so far has been done in mice, as the researchers noted that solid tumors in humans are far more complex. Human tumors can evolve and lose the targets that treatments are designed to recognize, raising the risk of the cancer escaping detection and continuing to grow.
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Long-term safety and side effects in humans are unknown ahead of clinical trials.
The researchers also noted that making big batches of identical, safe cells poses logistical and regulatory challenges.
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