Survival rates for pancreatic cancer have seen little improvement in the long term, with most patients having only a few months to live after diagnosis. This makes any breakthrough extremely important. This new therapy, called CAR-T cell therapy, trains the patient's own immune cells to track and attack cancer cells, offering the potential to change this situation.
Pancreatic cancer originates from the pancreas, an organ responsible for digestion and blood sugar control. Most cases are only discovered after the cancer has spread, making treatment extremely difficult. Once surgery is no longer an option, the only remaining treatment is usually a combination of multiple chemotherapy drugs, but even then, most patients survive less than a year after diagnosis. CAR-T therapy involves isolating immune cells from the blood, culturing and engineering them, and then reinfusing them into the body. This has proven quite effective in treating blood cancers, but it faces significant challenges in treating solid tumors such as pancreatic cancer.
Pancreatic tumors often form thick fibrous tissue walls and grow abnormal blood vessel structures, hindering the entry of immune cells. On the other hand, cancer cells lack clear and stable specific markers, and healthy cells are sometimes too similar to cancer cells, making it difficult for immunotherapy to "target only the bad cells and not harm the good ones," increasing the risk of damaging normal tissues. In addition, tumor cells may evolve over time, losing the markers originally targeted by the therapy, further evading the immune system's detection.
To overcome these challenges, next-generation CAR-T therapies employ engineered designs that allow immune cells to simultaneously target multiple antigens. This "dual-antigen" or "multi-antigen" strategy targets various markers commonly found in pancreatic cancer cells, including PRAME, SSX2, MAGEA4, NY-ESO-1, and Survivin. In this way, even if the tumor attempts to evade detection by hiding or altering some of these markers, CAR-T cells still have a better chance of successfully finding and attacking the cancer cells.
This novel immunotherapy is currently in clinical trials. The research team engineered the patient's own immune cells into CAR-T cells capable of recognizing the five major antigens mentioned above. Laboratory analysis revealed that most pancreatic tumors express at least two of these five markers, increasing the likelihood that the therapy will remain effective even if the tumor loses a target. Early results show that the therapy has a good safety profile, with some patients experiencing better survival than with standard treatment, and the level of detectable T cells in the tumor remaining relatively high after treatment. The research is also evaluating the effectiveness of combining this therapy with other treatments, such as chemotherapy, or drugs that help immune cells enter the tumor more effectively.
In the long run, these therapies are expected to move towards greater precision and personalization, designed to target specific combinations of tumor markers for each patient to improve efficacy and reduce side effects. However, larger-scale and longer-term clinical trials are still needed to confirm whether they can truly improve overall survival and to clarify which patient groups will benefit most. So far, the trial results have exceeded the research team's initial expectations, showing that by simultaneously targeting multiple tumor-related markers, cancer cells are less likely to escape immune surveillance. For pancreatic cancer patients with limited options, this is not only an important advance but may also lay the foundation for more innovative therapies in the future.
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