New cancer treatment seeks out deadly tumors and eliminates them
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Scientists at UCLA have developed an “off-the-shelf” cell-based immunotherapy that can track and kill pancreatic cancer cells even after they have spread to other organs.
In a study in mice, the treatment slowed cancer growth, prolonged survival and remained effective even in the harsh environment of solid tumors.
Lead author Dr. D., a postdoctoral researcher at UCLA. “Even if the cancer tries to evade a path of attack by changing its molecular signature, our treatment attacks it from multiple angles simultaneously. The tumor cannot adapt fast enough,” Yanruide Li said in a press release.
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To create the therapy, researchers took human stem cells and transformed them into a special immune cell called an invariant natural killer T cell (or NKT cell).
They then genetically modified these cells by adding a CAR receptor (chimeric antigen receptor), which allows the cells to recognize and attack pancreatic cancer cells.
UCLA scientists have created an off-the-shelf CAR-NKT cell therapy that kills pancreatic tumors in multiple preclinical models. (iStock)
According to the researchers, NKT cells are naturally compatible with any immune system, meaning they can enter the body without causing dangerous reactions. They can also be mass produced using any donated blood stem cells.
“One donor can provide enough cells for thousands of treatments,” according to the press release, potentially offering a more affordable and accessible approach.
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The team tested the therapy in several laboratory models. These included models in which the cancer was placed directly in the pancreas and models designed to mimic how the disease spread to other organs, such as the liver and lungs.
The researchers found that CAR-NKT cells were able to move into the tumor instead of being stuck outside, as is the case with many immune treatments.
The researchers emphasized that a single dose could cost around $5,000, much lower than personalized CAR-T treatments. (iStock)
Once inside the body, these engineered immune cells can detect 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 instead of burning out, these engineered cells keep working, allowing them to continue fighting the cancer longer.
The findings were published in the journal PNAS (Proceedings of the National Academy of Sciences).
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senior author Dr. D., professor of microbiology, immunology and molecular genetics at UCLA. “Developing an off-the-shelf therapy that targets both the primary tumor and its metastases in preclinical studies represents a fundamental shift in how we can treat this disease,” Lili Yang said in the same press release.
One dose could cost around $5,000, much less than personalized CAR-T treatments, the researchers noted.
The therapy could be mass produced from donor stem cells, potentially lowering cost and expanding access. (iStock)
According to researchers, pancreatic cancer is known to be aggressive and difficult to treat. Many patients are not diagnosed before the disease has spread, and the biology of the tumor creates numerous physical and chemical barriers that weaken the effectiveness of conventional treatments.
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Because the therapy targets a protein common in breast, ovarian and lung cancers, the same cell product could potentially treat more than one type of cancer.
In separate studies, the team has already proven the treatment’s effectiveness against triple-negative breast cancer and ovarian cancer.
Many patients are not diagnosed before the disease has spread, and the biology of the tumor creates numerous physical and chemical barriers that weaken the effectiveness of conventional treatments. (iStock)
Based on the initial findings, UCLA researchers are preparing to submit an application to the Food and Drug Administration to initiate human trials.
“We have developed a potent, safe, scalable and affordable therapy,” Yang said in the statement. “The next critical step is to prove that it can produce the same results in patients we saw in our preclinical studies.”
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All tests so far have been done on mice, as the researchers note that solid tumors in humans are much more complex. Human tumors can evolve and lose the targets that treatments are designed to recognize, increasing the risk that the cancer will escape detection and continue to grow.
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Long-term safety and side effects in humans are unknown prior to clinical trials.
The researchers also noted that producing large amounts of identical, safe cells poses logistical and regulatory challenges.
