A groundbreaking approach to cancer treatment discovered by Israeli researchers may soon allow tumors to expose themselves to the immune system, significantly enhancing the effectiveness of immunotherapy, according to The Press Service of Israel (TPS-IL).
This strategy paves the way for the development of new cancer-fighting drugs while expanding immunotherapy possibilities for certain patients.
Scientists from the Weizmann Institute and Stanford University found a way to force tumors to produce abnormal proteins, making them visible to immune cells. In laboratory models, this new method triggered a robust immune response capable of destroying tumors and slowing their growth. The findings were recently published in the peer-reviewed Cancer Cell journal.
Immunotherapy enlists the immune system to fight tumors. However, fewer than 57 percent of cancer patients are currently candidates for immunotherapy, and only about 20 percent respond effectively. Cancer cells often evade detection by presenting very few identifiable markers. The Israeli researchers sought to change that.
“The disrupted proteins don’t always result from a mistake in the DNA ‘recipe’ — that is, a mutation,” explained Prof. Yardena Samuels, who led the research. “They can also stem from a fault in the production process itself, known as translation. In our new study, we decided to investigate whether we could increase the number of targets for identifying and destroying cancer cells by intentionally interfering with the translation process.”
The translation process is how cells build proteins, with the ribosome assembling amino acids based on genetic instructions. Any misreading of these instructions can result in abnormal proteins.
However, the research team, including Chen Weller and Dr. Osnat Bartok from Samuels’s lab and Dr. Christopher S. McGinnis from Stanford University, used genetic engineering to delete an enzyme responsible for ensuring accurate translation. Without this enzyme, cancer cells produced faulty proteins that had never been seen before.
The team identified 34 short proteins that were uniquely synthesized in cancer cells following this disruption. These proteins became new targets for the immune system, allowing it to recognize and attack the cancerous cells. “Since the translation process is the same across cell types, a treatment that disrupts it in one cancer could work against many others,” Samuels explained.
The researchers then tested this approach in a mouse model of melanoma. They found that disrupting translation significantly increased the number of killer T cells capable of penetrating the tumor environment. However, these immune cells became exhausted before they could eliminate the cancer, a common challenge in immuno-oncology.
To overcome this, the team combined their approach with existing immunotherapy treatments designed to counteract tumor-induced immune suppression.
The results were striking.
“An existing type of immunotherapy that was not at all effective against the kind of melanoma we tested suddenly became very effective when tested in mouse models after the translation process in the mice’s cancer cells was disrupted,” Samuels said. “This combined treatment managed to eradicate or greatly reduce the tumor in around 40 percent of the mice.”
Currently, oncologists prioritize immunotherapy for patients whose tumors carry many mutations. However, the study found that low levels of the translation-regulating enzyme could predict a tumor’s susceptibility to immunotherapy, even in cases with few mutations.
“Finding a new predictive measure for the effectiveness of immunotherapy will allow doctors to offer the treatment to patients who, until now, were not candidates,” said Samuels.
The study could significantly impact cancer treatment. By forcing cancer cells to expose more immune targets, this approach could make immunotherapy effective for patients whose tumors previously had too few mutations to respond to treatment.
Doctors could use levels of the translation-regulating enzyme as a biomarker to predict which patients might benefit from immunotherapy, even if their tumors have few genetic mutations. This could lead to more personalized cancer treatments.
Because the translation process is similar across different cancer types, this strategy could be applied to melanoma, breast cancer, pancreatic cancer, and colorectal cancer. If proven effective, it could become a universal method to improve immunotherapy outcomes.
Targeting the translation process also opens a door to new drugs that intentionally disrupt protein production in cancer cells.
The researchers are using AI to identify additional translation-related targets in cancer cells.
The researchers are now exploring whether this approach could be applied to other cancers. Given that fewer than 57 percent of cancer patients are currently candidates for immunotherapy, and only about 20 percent respond effectively, this new method offers hope to many who previously had limited treatment options.
