Researchers have developed an mRNA cancer vaccine they suggest could help treat the common but deadly brain cancer glioblastoma, which affects about three in every 100 000 people worldwide each year.
Generally, people with this condition have an average survival length of about a year.
The scientists from the University of Florida say the new vaccine could retrain the body’s immune system to attack and potentially treat glioblastoma, cases of which are on the rise in many parts of the world due to ageing populations and environmental factors like air pollution.
Glioblastoma is a particularly challenging cancer to treat and has an average five-year survival rate of 6.9%, reports MedicalNewsToday.
The results of this study were published in the journal Cell.
“Glioblastoma is the most common malignant brain tumour, and despite medical innovations, outcomes have not precipitously changed in decades,” said lead author Elias Sayour, MD, PhD, the Stop Children’s Cancer/Bonnie R Freeman Professor for Paediatric Oncology Research at the University of Florida.
“Our brain tumour programme has developed promising effects with other forms of immunotherapy against brain cancer and wanted to test a novel mRNA vaccine design to enhance responses for these difficult-to-treat diseases.”
Benefits of personalised mRNA cancer vaccines
Ever since the mRNA vaccines were developed to fight the coronavirus, scientists have been studying their use for the treatment of other conditions, including cancer.
In this study, researchers used study participants’ own tumour cells to create a personalised vaccine for their particular cancer.
“mRNA is the information from our genetic code that is turned into protein: the hardware that makes each of us – and each cancer – unique,” Sayour said.
“By targeting the unique mRNA repertoire of a patient’s cancer, we can make exquisitely personalised vaccines unique to individual tumours in a manner that is feasible to all.”
Triggers effective immune response
The study evaluated the impact of the new mRNA vaccines by testing 10 pet dogs who had natural brain tumours and were enrolled in the study by their owners because they had no other treatment options.
Dogs treated with the mRNA cancer vaccine lived an average of 139 days, compared with the average 30- to 60-day survival rate for dogs with the condition.
After animal tests, the scientists expanded their research to a small FDA-approved clinical trial of four human study participants with glioblastoma.
After receiving the mRNA vaccine, researchers reported that in less than 48 hours, they were able to observe brain tumours moving from a “cold” silenced immune response to a “hot” active immune response.
“This is significant because it usually takes time, weeks to months with boosters, for vaccines to begin working,” Sayour said. “We expect this work to create a new paradigm that rapidly activates the immune system against cancer.
“To win the war on cancer, the immune system needs a better head start. We hope this approach gives the immune system the jump start it needs to win the race against rapidly evolving tumours. By getting rapid responses from a single vaccine, the immune system can be rapidly reprogrammed to fight cancer.”
Larger trials could validate findings
Scientists said that while it is still too early to assess the clinical effects of the mRNA cancer vaccine, they did report that human study participants receiving the vaccine either lived disease-free longer than expected or survived longer than expected.
The small clinical trial of just four participants also helped demonstrate early safety and feasibility before expanding to a larger clinical trial, said the researchers.
“We must validate these findings in (a) larger cohort of patients, identify a maximally tolerated dose, and begin phase 2 trials,” Sayour said.
“We are also moving aggressively to launch this platform against paediatric brain tumours.”
More research needed
Wael Harb, MD, haematologist and medical oncologist at MemorialCare Cancer Institute in Orange County, said: “The overall strategy is interesting – using the systemic immune response while reprogramming the tumour microenvironment is very promising – and in the larger context of immunotherapy research, is an exciting approach.
“The next step would be (a) well-designed clinical trial looking at the safety and efficacy in a more diverse patient population to really understand how these RNA-LPAs (RNA lipid-particle aggregates) work in reprogramming the tumour microenvironment. I would love to see, apart from safety efficacy data, biomarkers to show this is happening.”
Jose Carrillo, MD, neuro-oncologist at Pacific Neuroscience Institute and associate professor at the Saint John’s Cancer Institute in Santa Monica, who was also not involved in the study, was “cautiously optimistic” about the findings.
“This is a novel technique for inducing an immune response in glioblastoma …notoriously difficult to obtain significant advances in survival with immune therapies and clinical trials. Based upon studies like these, steady progress is being made in unravelling new discoveries that will get us one step closer to better treatments for our patients.”
Study details
RNA aggregates harness the danger response for potent cancer immunotherapy
Hector Mendez Gomez, Anna DeVries, Elias Sayour et al.
Published in Cell on 9 May 2024
Summary
Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumour microenvironment (TME). Here, we create “onion-like” multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumour mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumour models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became “hot” within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.
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