Cancer cells can be stealth like in their ability to evade attack from the immune system. This allows tumours to flourish and spread. The implantation of material into the body to target an immune response offers a promising alternative to the injection of cells manipulated ex vivo, but it involves a surgical procedure. Now a team of researchers from Harvard University have developed an injectable three-dimensional vaccine that works by triggering an immune response. This technology could form the basis of future treatments for a range of diseases, including cancer and HIV.
“We can create 3D structures using minimally–invasive delivery to enrich and activate a host’s immune cells to target and attack harmful cells in vivo,” said the study’s senior author David Mooney of Harvard University.
Tiny biodegradable rod-like structures made from silica, known as mesoporous silica rods (MSRs), can be loaded with biological and chemical drug components and then delivered by needle just underneath the skin. The rods spontaneously assemble at the vaccination site to form a three-dimensional scaffold. Dendritic cells can be recruited into the spaces within the scaffold. These cells perform a ‘surveillance’ function that monitors the body and triggers an immune response when a harmful presence is detected.
“Nano–sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron–sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells,” said Jaeyun Kim, the study’s co-lead author.
Synthesized in the lab, the MSRs contain nanopores that can be filled with specific cytokines, oligonucleotides, protein antigens or any variety of drugs of interest to allow a vast number of possible combinations to treat a range of infections. In this study the Harvard team incorporated the cytokine GM-CSF into the scaffold to stimulate dendritic cell recruitment and proliferation.
Although the team are currently focusing on developing a cancer vaccine, this technology could potentially be used across a number of conditions by varying the cytokines released from the MSRs to recruit different types of cells to the scaffolds. The team anticipate that by tuning the surface properties and pore size of the MSR to control the release of various molecules from the nanopores on the scaffold, that they may be able to manipulate the immune system to treat multiple diseases.
Once dendritic cells from the body have invaded the scaffold structure the combination of drugs contained with the MSRs are released, activating the dendritic cells and initiating an immune response. The activated dendritic cells in the experimental mouse host were observed to leave the scaffold and home to the lymph nodes, where they coordinated a powerful immune response. At the site of injection, the MSRs biodegraded and dissolved naturally within a few months.
The researchers also observed that injection of the MSR-based vaccine formulation enhanced systemic helper T cells TH1 and TH2 serum antibody and cytotoxic T-cell levels compared to controls. These findings suggest that injectable MSR may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.
“We anticipate 3D vaccines could be broadly useful for many settings, and their injectable nature would also make them easy to administer both inside and outside a clinic,” said Mooney. Since the vaccine works by triggering an immune response, the method could even be used preventatively by building the body’s immune resistance prior to infection.
So far, the researchers have only tested the 3D vaccine in mice and further studies would be essential to see how well these molecules are tolerated in humans. In order to target the vaccine for different diseases detailed knowledge of the correct mix of cytokines and protein antigens to include within the scaffold would also be required.