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Technique Devised for 3-D Immunotherapy Injections

Mesoporous silica rods

Mesoporous silica rods or MSRs that assemble into a porous 3-D matrix (Wyss Institute, Harvard University)

9 December 2014. Biomedical engineers at Harvard University designed a biomaterial that in lab animals assembles into a three-dimensional framework for delivery of therapies triggering an immune response to treat cancer and infectious diseases. The team from the lab of David Mooney at Harvard’s Wyss Institute for Biologically Inspired Engineering published its findings yesterday in the journal Nature Biotechnology (paid subscription required).

Mooney and colleagues — including researchers from Harvard, affiliated research centers, and Sungkyunkwan University in Korea — were seeking an alternative to surgical transplants of cells cultured in the lab for therapies that harness the immune system to fight diseases, such as immunotherapy for cancer. The alternative in this case uses biodegradable silica rods that can be injected under the skin and form into a scaffold or matrix. The micro-scale silica rods are built with even smaller nanoscale pores that can be filled with agents, such as cytokines and other proteins, genetic material, or antigens that generate a therapeutic response from the immune system.

After injection, the silica rods spontaneously collect together under the skin at the injection site, much like a a pile of straws or matchsticks; see image at top. While not forming into a predetermined structure, the silica rods develop into enough of a matrix with micro-sized openings that allow for millions of dendritic cells — the kind that look for and capture antigens to trigger an immune response — to collect in those gaps.

After dendritic cells collect in the scaffold, the agents loaded in the porous slica rods are released that initiate the immune response. Once activated, the dendritic cells travel from the scaffold to the lymph nodes where T-cells in the immune system are directed to fight invading cancer cells or infectious microbes. The biodegradable silica rods at the injection site then begin to dissolve and are naturally removed.

The researchers tested the technique in lab mice injected with silica rods carrying a vaccine formulation. The team observed the matrix of silica rods collected dendritic cells that traveled to lymph nodes, and found the mice had higher T-cell levels after the injections indicating an immune response.

Graduate student and co-lead author Aileen Li says in a university statement that altering the surface properties and pore size of the mesoporous silica rods or MSRs makes it possible to program and control the release of therapeutic agents, thus making the technique applicable to a number of diseases. “Although right now we are focusing on developing a cancer vaccine,” notes Li, “in the future we could be able to manipulate which type of dendritic cells or other types of immune cells are recruited to the 3-D scaffold by using different kinds of cytokines released from the MSRs.”

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