Systemic RNA-LPA mRNA vaccines were feasible, generally tolerated, and rapidly activated immune programs in canine tumors.
Evidence
An open-label canine translational study treated 10 dogs with histologically confirmed glioma and measured manufacturing feasibility, tolerability, survival, cytokine responses, mRNA tumor localization, and immune gene signatures.
Caveat
The small nonrandomized canine study used historical palliative-care survival comparisons, so it cannot prove survival benefit or human efficacy.
Simplified
Malignant is considered invariably recalcitrant, thus necessitating development of new therapeutic approaches. Spontaneously arising canine glioma exhibits important molecular and pathological similarities to malignant pediatric glioma, making it an invaluable model for testing novel therapies. We evaluated safety and activity of RNA lipid particle aggregates (LPAs) designed to provoke cancer immunogenicity in 10 dogs with histologically confirmed glioma. Vaccine manufacturing was feasible in all subjects and generally well tolerated. Median survival time was 123 and 155 days in dogs receiving three (Group A) or four (Group B) vaccines, respectively; this was increased from historical reporting of subjects receiving palliative care. Responding animals had a robust cytokine response following infusions. In animals receiving non-specific RNA-LPAs, there was localization of messenger RNA (mRNA) payloads to the brain tumor microenvironment and a rapid shift in immunologic gene signatures consistent with a viral response. These data demonstrate the ability to induce rapid viremic response in the tumor microenvironment following a single peripherally administered . Since RNA-LPAs are amenable to repeat boosts, these formulations may overcome challenges of tumor immunosuppression and therapeutic access and are currently under evaluation in first-in-human trials (NCT04573140, NCT06389591).
Key numbers
123 days
Median Survival Time (Group A)
Survival time for dogs receiving three RNA-LPAs.
155 days
Median Survival Time (Group B)
Survival time for dogs receiving four RNA-LPAs.
26 days
Historical Survival Duration
Survival duration with palliative care alone.
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