A General Immune Boost Instead of a Specific Target

Most cancer immunotherapies rely on identifying and attacking neoepitopes—proteins that arise from mutations specific to a patient’s tumor. This approach works best in cancers with high mutation loads, such as melanoma, but has limited success in tumors with low mutational burden. A study published in Nature Biomedical Engineering and conducted by scientists at the University of Florida challenges that model.

In their experiments, researchers used an experimental mRNA vaccine delivered via lipid nanoparticles, similar to the technology used in COVID-19 vaccines. But instead of encoding a viral protein, this vaccine instructs the immune system to produce proteins that activate an immune response.

One of these proteins, PD-L1, is commonly found on cancer cells and helps them evade immune detection. By artificially inducing PD-L1 expression in tumors, the vaccine made the cancer cells more visible to the immune system, improving the effects of immune checkpoint inhibitors.

Making Resistant Tumors Respond to Treatment

In mouse models of melanoma, the mRNA vaccine cleared drug-resistant tumors and triggered “antigenic spreading”—a process where the immune system begins to recognize and attack multiple tumor-related antigens. In some cases, the vaccine worked even without additional treatments. It was also tested in models of brain, skin, and bone cancers with similarly promising results.

Researchers demonstrated that tumors resistant to checkpoint inhibitors lacked these early immune signals, but became sensitive when treated with RNA-loaded lipid particles that boosted interferon activity. This led to a broader immune reaction, enabling previously unresponsive tumors to respond to immunotherapy.

Together, these results highlight a new paradigm in cancer treatment: instead of customizing a vaccine to match each patient’s unique tumor profile, it may be possible to create a general-purpose vaccine that teaches the immune system to react aggressively to cancer, regardless of the tumor’s specifics.

Laying the Groundwork for an Off-the-Shelf Cancer Vaccine

Dr. Elias Sayour, a pediatric oncologist at the University of Florida and lead investigator on the study, described the results as “a proof of concept” that such a vaccine could eventually become an off-the-shelf solution. Co-author Dr. Duane Mitchell added that this approach may pave the way for more accessible and broadly applicable cancer treatments.

While these findings are based on animal studies, they offer a strong foundation for clinical research. If the vaccine proves effective in humans, it could significantly improve cancer immunotherapy, especially for patients with tumors that previously showed little to no response.

The research not only expands the potential use of mRNA technology beyond infectious disease but also underscores the power of immune system priming. As development continues, a universal cancer vaccine may soon become a powerful tool in the fight against one of the world’s most complex diseases.

[Source]

The post Universal Cancer Vaccine Shows Promise in Boosting Immunotherapy Response appeared first on Medical Journal Daily.

Globally, over 300,000 people are diagnosed with glioblastoma annually. This aggressive brain cancer originates from brain cells and, if untreated, spreads rapidly. The average survival time post-diagnosis is approximately 18 months. Traditional treatment options, such as radiotherapy, often lead to collateral damage to healthy cells, causing side effects like nausea, hair loss, and memory problems.

Radiodynamic therapy has emerged as a promising alternative, where patients receive specially designed compounds that generate cancer-killing free radicals when activated by X-rays. This method requires significantly lower X-ray doses—only about 20-30% of conventional radiotherapy doses. However, existing radiodynamic therapy compounds, which contain heavy metals, lack precision in targeting cancer cells and may harm healthy cells.

Prof. Pu’s team has developed a novel compound called the Molecular Radio Afterglow Dynamic Probe (MRAP), composed of biochemicals and iodine, free from heavy metals. This innovation aims to address the limitations of current radiodynamic therapy by ensuring precision in targeting cancer cells while reducing side effects.

In experiments with mice, MRAPs were directly injected into brain tumors and activated with X-rays. Remarkably, the required X-ray dosage was over six times lower than current methods. The MRAPs absorbed the X-ray radiation, generating cancer-killing free radicals only upon encountering a specific enzyme abundantly produced by brain tumor cells. This precision prevented the activation of MRAPs in normal cells, eliminating unintended side effects.

The NTU team’s experiments showed that MRAPs effectively halted tumor growth in mice, doubling their survival time from 37 to 76 days compared to untreated mice. Importantly, treated mice exhibited no tissue damage or weight loss, and the MRAPs were eventually excreted through urine and feces.

Prof. Pu highlighted the potential benefits of this method, stating, “We used very low dosages of X-rays and cancer-killing MRAPs. Also, the anti-cancer compounds were active only in the brain tumor and not healthy cells. So, we expect our treatment method to be safer and have fewer side effects than existing ones.”

A patent has been filed for MRAPs, and Prof. Pu’s team is in discussions with potential investors. The findings from this study have garnered attention from experts like Professor Marc Vendrell from The University of Edinburgh, who praised the research as a significant advancement in combining X-rays and light for precise tumor treatment.

Looking ahead, Prof. Pu’s team plans to enhance MRAPs to further improve their targeting capabilities and incorporate cancer-curbing functions such as immunotherapeutic abilities. These enhancements aim to activate the immune system to combat cancer cells and prevent recurrence.
Broader Implications

Earlier research by the team, published in Nature Biomedical Engineering in December 2022, demonstrated that another type of anti-cancer compound developed by the scientists, energized by ultrasound instead of X-rays, successfully inhibited new cancer cell growth in mice. This finding was linked to the activation of the mice’s cancer-fighting immune cells.

The development of MRAPs marks a significant milestone in brain cancer treatment, offering a safer, more precise alternative to traditional radiotherapy. With ongoing research and potential clinical applications on the horizon, this innovation holds promise for improving the quality of life and survival rates for glioblastoma patients worldwide.

Details of the study can be found in “Molecular radio afterglow probes for cancer radiodynamic theranostics” in Nature Materials (2023) and “Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics” in Nature Biomedical Engineering (2022).

References:

1. Nature Materials. “Molecular radio afterglow probes for cancer radiodynamic theranostics.” Nature Materials News Release, 2023. Available from: https://www.nature.com/articles/s41563-023-01659-1.
2. Nature Biomedical Engineering. “Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics.” Nature Biomedical Engineering News Release, 2022. Available from: https://www.nature.com/articles/s41551-022-00978-z.

The post Low-Dose X-Rays Energize New Compounds to Eliminate Brain Cancer Cells appeared first on Medical Journal Daily.