In what researchers are calling a major leap forward in cancer immunotherapy, scientists have developed an innovative mRNA-encoded nanobody therapy that shows powerful promise against colorectal cancer — one of the world’s most common and deadliest malignancies. This breakthrough combines advanced genetic delivery systems with tiny, highly targeted immune modulators to tackle a cancer type that has traditionally resisted modern immunotherapy approaches.
Colorectal cancer ranks among the top three cancers globally and is a leading cause of cancer-related fatalities. While treatments such as surgery, chemotherapy, and radiation have improved survival for some patients, many still face limited options, especially those with microsatellite stable tumors — the subtype most resistant to immune checkpoint drugs. These resistance issues have driven scientists to search for better ways to activate the immune system directly against tumors.
The new approach leverages messenger RNA (mRNA) — the same genetic messaging technology behind recent vaccines — to instruct the body’s own cells to produce nanobodies that target PD-L1, a molecule tumors use to hide from immune attacks. Unlike standard monoclonal antibodies, which are large, expensive, and often fail to penetrate deeply into solid tumors, these nanobodies are about one-tenth the size and can reach deeper within tumor tissue with greater efficiency and fewer side effects.
In preclinical studies conducted by a team including scientists from the John A. Burns School of Medicine (JABSOM), the mRNA nanobody therapy delivered via lipid nanoparticles significantly suppressed tumor growth in mouse models of both sporadic and colitis-associated colorectal cancers. Notably, tumor progression was markedly reduced after repeated treatment, and the formulation designed to prolong nanobody circulation demonstrated especially robust effects.
This technology uses lipid nanoparticle (LNP) carriers to safeguard and transport the mRNA into cells — similar to the delivery systems used for mRNA vaccines against infectious diseases. Once inside, the body’s cells read the mRNA instructions and generate nanobodies that bind to PD-L1 on cancer cells. This blocks the immune-evading action of PD-L1 and unmasks the tumor to the immune system, allowing T-cells to recognize and attack it more effectively.
What makes this approach especially exciting is its potential to overcome a long-standing hurdle in colorectal cancer treatment. Traditional immunotherapies targeting PD-1/PD-L1 checkpoints have transformed therapies for melanoma, lung cancer, and other cancers — but have shown disappointing results in most colorectal cases, especially the aggressive microsatellite stable subtype. By turning the body into a nanobody factory, this method bypasses limitations of fixed-structure antibody drugs and may provide broader, more effective immune activation.
Beyond enhanced tumor penetration and improved immune engagement, the nanobody platform may also cut costs substantially. Conventional antibody therapies can cost patients hundreds of thousands of dollars per year, while mRNA-based technologies, produced at scale, could offer more affordable cancer treatment options if translated successfully into humans.
Researchers stress that although these results are currently preclinical, the promising data calls for accelerated efforts toward clinical trials in humans. If the technology proves safe and effective in patients, it could represent a paradigm shift for cancers historically unresponsive to immune-based therapies. The study’s success also underscores a broader trend in medical research where mRNA isn’t just a vaccine tool but a versatile therapeutic platform for serious diseases like cancer.
In summary, mRNA-encoded nanobodies may soon become a game-changing weapon in the fight against colorectal cancer, offering renewed hope for patients with resistant tumors and expanding the frontier of immunotherapy beyond its current limits.
