RNA-LPAs: the latest breakthrough in immuno-oncology?
Researchers have sought to overcome the limitations of current cancer vaccines by developing a mRNA vaccine wrapped into a vesicle within an ‘onion-like’ structure.
To tackle the limitations of current cancer vaccines, scientists from the University of Florida Health (FL, USA) designed multi-lamellar RNA lipid-particle aggregates (RNA-LPAs), a delivery tool that allows for increased payload to the tumor site. The novel approach has demonstrated promising results in its first-in-human trial.
mRNA vaccines have proved greatly successful in the battle against infectious diseases. However, when it comes to cancer, they face the same obstacles that checkpoint inhibitors and CAR-T encounter, including an immunosuppressive tumor microenvironment (TME) and restricted antigenicity, due to the limited amount of mRNA payload that can be packaged per particle.
“Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions… And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would,” explained senior author Elias Sayour (University of Florida Health).
The mRNA vaccine has been tested in murine and canine trials, for the latter it was shown to improve survivorship and reprogram the TME, making the TME ‘hot’ after a single infusion. In its first-in-human trial, the vaccine demonstrated further promising results, including reprograming the TME and eliciting adaptive immunity for glioblastoma patients.
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“Among the most impressive findings was how quickly the new method, delivered intravenously, spurred a vigorous immune-system response to reject the tumor. In less than 48 hours, we could see these tumors shifting from what we refer to as ‘cold’ — immune cold, very few immune cells, very silenced immune response — to ‘hot,’ very active immune response,” commented Sayour.
A key allure of this RNA-LPA vaccine technique is that it can be highly personalized to the individual patient. For the handful of patients included in the initial human trial, RNA was extracted from their own tumor. Next, the patient’s mRNA was amplified and wrapped into biocompatible lipid nanoparticles, enabling for earlier, enhanced immune activation.
The next steps for the vaccine involve a Phase I clinical trial, comprising up to 24 adult and pediatric patients. Following that, the team plan to collaborate with Pediatric Neuro-Oncology Consortium to deliver more personalized vaccines across children’s hospitals within the USA.