Editors' ChoiceIMMUNOBIOENGINEERING

Lymph Nodes “On Demand”

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Science Translational Medicine  14 Jan 2015:
Vol. 7, Issue 270, pp. 270ec8
DOI: 10.1126/scitranslmed.aaa5546

If cancer isn’t detected before it metastasizes, interventions like radiation and chemotherapy are less likely to be effective. Fortunately, we have an immune system that is innately able to combat the disease—but only after it receives the right stimulation. For example, vaccines are able to train lymphocytes to fight off cancer. But, like other immune-conditioning regimens, vaccines work slowly and may not elicit responses strong enough to counter tumors after they take foot.

Harvard scientists described a new way to promote innate anticancer responses based on biomaterials that self-assemble into structures supporting cancer-targeting immune cells. Their idea was to create tiny “mesoporous silica rods” (MSRs) that, after subdermal injection into mice exhibiting EL4 lymphoma, spontaneously assembled into three-dimensional, niche-like microenvironments. They engineered the MSRs to slowly release trophic factors (in particular, GM-CSF and the CpG-oligodeoxynucleotide “danger signal”), which attracted and matured circulating dendritic cells. After entering the porous niche created by the MSRs, the dendritic cells encountered tumor antigens engineered into the matrix, which enabled them to prime tumor-specific T lymphocytes and antibody responses against the lymphoma.

It is too early to judge their therapeutic value, but three-dimensional (3D) vaccines could provide many benefits compared with other anticancer interventions. For example, various bioengineering strategies that mobilize the immune system to combat disease—nanoparticle vaccines, vaccine patches, and microparticles that mimic antigen-presenting cells, to name a few—have already entered clinical testing; but all of them depend on lymphoid organs to prime immune responses. By contrast, the MSR-based vaccine intrinsically forms a “synthetic organ” to house and modulate the very cells that can orchestrate a reaction against cancer. This approach could provide a distinct advantage in the anticancer arena, where proliferating tumor cells tend to suppress the usual niches involved in priming immune responses.

J. Kim et al., Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64–72 (2015). [Full Text]

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