Abstract
Recent studies have shown that intradermal vaccination has great potential for T cell-mediated cancer immunotherapy. However, classical intradermal immunization with a hypodermic needle and syringe has several drawbacks. Therefore, in the present study a digitally controlled hollow microneedle injection system (DC-hMN-iSystem) with an ultra-low dead volume was developed to perform micro-injections (0.25–10μL) into skin in an automated manner. A synthetic long peptide derived from human papilloma virus formulated in cationic liposomes, which was used as a therapeutic cancer vaccine, was administered intradermally by using the DC-hMN-iSystem. Fused silica hollow microneedles with an inner diameter of 50μm and a bevel length of 66±26μm were successfully fabricated via hydrofluoric acid etching. Upon piercing these microneedles into the skin using a protrusion length of 400μm, microneedles were inserted at a depth of 350±55μm. Micro-injections of 1–10μL had an accuracy between 97 and 113% with a relative standard deviation (RSD) of 9%, and lower volumes (0.25 and 0.5μL) had an accuracy of 86–103% with a RSD of 29% in ex vivo human skin. Intradermal administration of the therapeutic cancer vaccine via micro-injections induced strong functional cytotoxic and T-helper responses in mice, while requiring much lower volumes as compared to classical intradermal immunization. In conclusion, by using the newly developed DC-hMN-iSystem, very low vaccine volumes can be precisely injected into skin in an automated manner. Thereby, this system shows potential for minimally-invasive and potentially pain-free therapeutic cancer vaccination.
Highlights
The activation of the T-cells is necessary to elicit tumor destruction in therapeutic cancer vaccination [1,2,3,4]
After in vivo administration of an synthetic long peptide (SLP) vaccine dendritic cells can internalize the SLPs, and subsequently process and present the cytotoxic and helper T-cell epitopes through major histocompatibility complexes (MHC) class I and class II molecules, respectively [1,2]
Our study shows that the dose that is intradermally delivered via micro-injections of 1–10 μL is controllable as the delivery via a classical hypodermic needle and syringe
Summary
The activation of the T-cells is necessary to elicit tumor destruction in therapeutic cancer vaccination [1,2,3,4]. Therapeutic cancer vaccination based on tumor specific peptides holds the potential for tailormade immunotherapy [1,2]. The sequences of these peptides are based on tumor antigens and contain, ideally both, a cytotoxic (CD8+) and a helper (CD4+) T-cell epitope. The incorporation of both sequences into a synthetic long peptide (SLP) is a proven strategy to trigger a cellular immune response directed towards the tumor. Dendritic cells are the main key in processing and presenting antigens to T-cells to provoke T-cell immune responses [5,6,7]. After in vivo administration of an SLP vaccine dendritic cells can internalize the SLPs, and subsequently process and present the cytotoxic and helper T-cell epitopes through major histocompatibility complexes (MHC) class I and class II molecules, respectively [1,2]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call