Researchers at the Massachusetts Institute of Technology (MIT) and its Koch Institute for Integrative Cancer Research recently revealed a new device that offers new possibilities in the field of cell-based vaccines. The study is entitled “Microfluidic squeezing for intracellular antigen loading in polyclonal B-cells as cellular vaccines” and was published in the journal Scientific Reports.
Antigen presenting cells correspond to a subset of immune cells (like B cells and dendritic cells) that are able to capture foreign or self-proteins, process them into peptides (antigens) and present them to immune T cells, activating them and mounting an inflammatory or tolerogenic immune response against these antigens.
Vaccines based on antigen presenting cells, where the patient’s own immune cells are reprogrammed to fight foreign invaders, have been considered a promising strategy in diseases like cancer and viral infections. The majority of these cell-based vaccines are developed based on dendritic cells, but several issues have impaired their translation into a clinical setting.
Immune B cells are also promising candidate vaccine antigen presenting cells. They are abundant in circulation and able to proliferate when activated, however, B cells have a limited ability to acquire and process antigens for subsequent T cell activation.
“We wanted to remove an important barrier in using B cells as an antigen-presenting cell population, helping them complement or replace dendritic cells,” explained the study’s first author Dr. Gregory Szeto in a news release.
In the study, the team showed that through the use of a microfluidic cell-squeezing device developed at MIT, called CellSqueeze, it is possible to introduce specific antigens inside B cells, offering a new strategy for the development and implementation of antigen-presenting cell vaccines based on B cells. In simple terms, the device works by applying a gentle pressure to B cells, squeezing them and consequently allowing the opening of small, temporary holes in their membranes so that target antigens can be inserted by diffusion. Using mice, researchers showed that these squeezed B cells were able to induce the expansion of antigen-specific T cells.
“The antigen-presenting capabilities of B cells have often been underestimated, but they are being increasingly appreciated for their practical advantages in therapies,” said Dr. Gail Bishop from the University of Iowa Carver School of Medicine, who was not involved in this study. He mentions that this “creative new approach with considerable potential in the development of antigen-presenting cell vaccines (…) permits loading B cells effectively with virtually any antigen and has the additional benefit of targeting the antigens to the CD8 T-cell presentation pathway, thus facilitating the activation of the killer T cells desired in many clinical applications.”
“Our dream is to spawn out a whole class of therapies which involve taking out your own cells, telling them what to do, and putting them back into your body to fight your disease, whatever that may be,” said Armon Sharei who was involved in the development of CellSqueeze technology. “We envision a future system, if we can take advantage of its microfluidic nature, as a bedside or field-deployable device, (…) Instead of shipping your cells off to this big, centralized facility, you could do it in your hospital or your doctor’s office.”
“Down the road, you could potentially get enough cells from just a normal syringe-based blood draw, run it through a bedside device that has the antigen you want to vaccinate against, and then you’d have the vaccine,” added Dr. Szeto.
The team’s next goal is to improve their B cell-based vaccine and turn it into a more effective and less expensive method for cell-based therapies for patients.
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