Induction of potent antitumor immunity by intradermal DNA injection using a novel needle‐free pyro‐drive jet injector

Abstract

The current success of mRNA vaccines against COVID‐19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle‐free pyro‐drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA‐expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA‐specific CD8 + T‐cell expansion in lymph node cells. Increased mRNA expression of both interferon‐γ and interleukin‐4 and an enhanced proliferative response of OVA‐specific CD8 + T cells, with fewer CD4 + T cells, were also observed. OVA‐specific in vivo killing of the target cells and OVA‐specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA‐expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA‐expressing E.G7‐OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA‐expression plasmid DNA using the PJI showed a stronger CTL‐dependent prophylactic effect. These results suggest that the novel needle‐free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA‐specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses.

Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development

“…At present, needle-free drug delivery technology is advancing towards high-capacity delivery, self-care, and gene therapy. Needle-free thermoresponsive jet injectors have been shown to effectively deliver plasmid DNA to the skin, resulting in higher protein expression compared to needle injectors [217]. Large-capacity subcutaneous needle-free syringes have an injection tolerance of up to 2.0 mL, and the injection effect is generally better than two separate 1.0 mL injections using a needle-free injection system [218].…”

A Promising Needle-Free Pyro-Drive Jet Injector for Augmentation of Immunity by Intradermal Injection as a Physical Adjuvant

“…Very recently, a novel needle-free PJI called Actranza TM lab (Daicel Corporation, Osaka, Japan) (Figure 3) has been developed, which has a unique characteristic in that the PJI utilizes gunpower as a mechanical driving force, and in particular bi-phasic pyrotechnics to induce high jet velocity and the wide dispersion of the injected plasmid DNA solution into the skin and muscle of mice, rats, pigs and humans [42][43][44][45][46][47][48][49][50][51]. The pyrotechnic technology was previously developed and initially utilized in the inflator products in an airbag [52] (https://www.daicel.com/safety/en/inflator/, accessed on 1 April 2023).…”

“…In a cancer experimental model, ovalbumin (OVA) was commonly used as an antigen, and the inoculation of C57BL/6 mice with tumor cells that were stably transfected with the OVA-expression vectors (lymphoma E.G7-OVA or melanoma B16F10-OVA) induced OVA-specific cellular and humoral immune responses. In a comparative study between the PJI and a needled syringe, the effectiveness of the induction of OVA-specific cellular and humoral immune responses by intradermal injection of OVA-expression plasmid (pOVA obtained from Addgene) was examined [50]. After a single intradermal injection of OVAexpression plasmid, OVA-specific cytotoxic CD8 + T cells (CTLs) were rapidly generated within 2 weeks, which was detected by a tetramer assay using flow cytometry.…”

Jet injection potentiates naked mRNA SARS-CoV-2 vaccine in mice and non-human primates by adding physical stress to the skin

“…Herein, we used a novel needle-free, pyro-drive liquid jet injector (PYRO) ( 28 ) to deliver naked mRNA instantaneously and efficiently in the skin before considerable mRNA degradation. According to previous research, PYRO enhanced plasmid DNA (pDNA) delivery to rodent skin, providing efficient vaccination effects ( 29–31 ). Interestingly, in the present study, PYRO effectively delivered naked mRNA in the skin of rodents and NHPs, despite a 100-fold faster mRNA degradation rate by nucleases in extracellular fluids than pDNA ( 32 ).…”