用于增强静脉给药疫苗疗效的nanoprimer技术

The efficacy of intravenously (IV) administered therapeutic agents is often limited by hepatic clearance, resulting in reduced accumulation at the target site and in potential hepatotoxicity. Nanobiotix's innovative Nanoprimer technology aims to shift the balance of therapeutics' bioavailability and toxicity. The Nanoprimer is a biocompatible, engineered liposome that transiently occupies cells of the mononuclear phagocyte system, responsible for the clearance of nanoparticles. Administered shortly before the therapeutic agent, the Nanoprimer reduces the early elimination and increases bioavailability during the agent's critical window of activity. proofs of concept were realized with multiple modalities including nucleic acid-based products. Our latest research has expanded the evaluation of the Nanoprimer for enhancing the efficacy of cancer vaccines. The Nanoprimer's effect on antigen-specific CD8⁺ T cell responses was evaluated using 2 vaccine platforms: mRNA-loaded lipoplex encoding an ovalbumin epitope and ovalbumin peptide-loaded liposomes. De novo priming of CD8⁺ T cells was assessed 7 days post-immunization. To evaluate the functional activity of generated CD8⁺ T cells, splenocytes were restimulated ex vivo with the antigenic peptide for 24 hours, and IFN-gamma production was quantified. In a single-dose immunization study, using peptide-loaded liposomes, pre-treatment with the Nanoprimer resulted in a 6-fold increase in antigen-specific CD8⁺ T cells and a marked elevation of IFN-gamma production by splenocytes, indicative of a strong effector function. Similar studies using a single dose of mRNA-lipoplex demonstrated that the Nanoprimer dramatically enhanced the generation of antigen-specific CD8⁺ T cells, reaching up to 20% of the total CD8⁺ T cells. The expansion of antigen-specific CD8⁺ T cells was correlated with increased IFN-gamma secretion, consistent with functional cytotoxic activity. For the evaluation of the memory immune response, animals received a primary vaccination (three repeated injections of the vaccine at days 0, 7 and 14), and memory response was assessed on day 73 by measuring the frequency of antigen-specific CD8+ T cells, 3 days after the booster immunization. The Nanoprimer increased antigen-specific CD8+ T cell responses, reaching up to 54% of total CD8+ T cells for mRNA-lipoplex (compared to 27% with vaccine alone) and up to 27% for peptide-liposome (with no detectable response observed in the vaccine alone group). These findings demonstrate that the Nanoprimer can enhance acute and memory cellular immune responses across multiple vaccine modalities. Its ability to increase antigen-specific CD8⁺ T cell quantities and functional cytokine responses underscores its potential to improve the therapeutic index of cancer immunotherapies. Overall, Nanoprimer technology represents a promising strategy to unlock the full clinical potential of innovative therapies.