Three-Dimensional Vaccines Sensitize the Immune System to Cancer


Cancer has the capacity to fool the immune system and evade attack from immune cells. This act of immune system evasion allows tumors to grow and spread throughout the body without any resistance. A relatively new strategy called immunotherapy attempts to stimulate the patient’s immune system to mount an immune response against the tumor and sensitize it to the tumor. However, a new protocol developed by a research teams at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard’s School of Engineering and Applied Sciences (SEAS) uses a three-dimensional structure to program the immune system to attack and destroy tumors.

The senior author of this study, David Mooney, who is a Wyss Institute Core Faculty member and the Robert P. Pinkas Professor of Bioengineering at Harvard SEAS, described this new technique: “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.”

This 3-D structure consists of tiny, biodegradable rod–like structures made from silica, known as mesoporous silica rods (MSRs). These MSRs can be loaded with biological and chemical drug components, and then injected by needle just underneath the skin. These rods spontaneously assemble at the injection site to form a three–dimensional scaffold (think of pouring a box of match sticks into a pile on a table). The porous spaces between the MSRs are large enough to recruit and fill with dendritic cells. Dendritic cells are immune cells that play the part of surveillance cells that identify foreign cells and substances and trigger an immune response to those things identified as foreign.

Mesoporous silica rods (MSRs) spontaneously assemble to form a porous 3D scaffold, as seen in this SEM image. The 3D scaffold has many nooks and crannies and is large enough to house tens of millions of recruited immune cells. Credit: Wyss Institute at Harvard University
Mesoporous silica rods (MSRs) spontaneously assemble to form a porous 3D scaffold, as seen in this SEM image. The 3D scaffold has many nooks and crannies and is large enough to house tens of millions of recruited immune cells.
Credit: Wyss Institute at Harvard University

“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 co-lead author Jaeyun Kim, Ph.D., an Assistant Professor of Chemical Engineering at Sungkyunkwan University and a former Wyss Institute Postdoctoral Fellow.

MSRs are made in the lab with nanopores, which are small holes that can be filled with specific cytokines, oligonucleotides, large protein antigens, or any variety of drugs. Thus, these structures are excellent repositories that can present a vast range of possible combinations to treat a range of infections or stimulate the immune system to attack several different invading elements.

“Although right now we are focusing on developing a cancer vaccine, in the future we could be able to manipulate which type of dendritic cells or other types of immune cells are recruited to the 3D scaffold by using different kinds of cytokines released from the MSRs,” said co-lead author Aileen Li, a graduate student pursuing her Ph.D. in bioengineering at Harvard SEAS. “By tuning the surface properties and pore size of the MSRs, and therefore controlling the introduction and release of various proteins and drugs, we can manipulate the immune system to treat multiple diseases.”

Once the 3D scaffold has recruited dendritic cells from the body, the drugs contained in the MSRs are released. These drugs activate the dendritic cells and initiate an immune response. The activated dendritic cells then leave the MSR-based scaffolds and travel to the lymph nodes, where they raise alarm and direct the body’s immune system to attack specific cells, such as cancerous cells. Within a few months, the body naturally degrades the MSRs, and they dissolve and leave no trace of their presence.

To date, this team has only tested their 3D vaccines in mice, but these 3D vaccines have proven to be remarkably effective. Injectable 3D scaffolds recruited and attracted millions of dendritic cells in a host mouse, before dispersing the cells to the lymph nodes and triggering a powerful immune response.

These vaccines are easily and rapidly manufactured so that they could potentially be widely available very quickly in the face of an emerging infectious disease. “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 preventively by building the body’s immune resistance prior to infection.

“Injectable immunotherapies that use programmable biomaterials as a powerful vehicle to deliver targeted treatment and preventative care could help fight a whole range of deadly infections, including common worldwide killers like HIV and Ebola, as well as cancer,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D. who is also Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at Harvard SEAS. “These injectable 3D vaccines offer a minimally invasive and scalable way to deliver therapies that work by mimicking the body’s own powerful immune–response in diseases that have previously been able to skirt immune detection.”

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).