title: Engulfing tumors with synthetic extracellular matrices for cancer immunotherapy.
abstract: Local immunotherapies are under investigation for the treatment of unresectable tumors and sites of solid tumor resection to prevent local recurrence. Successful local therapy could also theoretically elicit systemic immune responses against cancer. Here we explored the delivery of therapeutic dendritic cells (DCs), cytokines, or other immunostimulatory factors to tumors via the use of 'self-gelling' hydrogels based on the polysaccharide alginate, injected peritumorally around established melanoma lesions. Peritumoral injection of alginate matrices loaded with DCs and/or an interleukin-15 superagonist (IL-15SA) around 14-day established ova-expressing B16F0 murine melanoma tumors promoted immune cell accumulation in the peritumoral matrix, and matrix infiltration correlated with tumor infiltration by leukocytes. Single injections of IL-15SA-carrying gels concentrated the cytokine in the tumor site approximately 40-fold compared to systemic injection and enabled a majority of treated animals to suppress tumor growth for a week or more. Further, we found that single injections of alginate matrices loaded with IL-15SA and the Toll-like receptor ligand CpG or two injections of gels carrying IL-15SA alone could elicit comparable anti-tumor activity without the need for exogenous DCs. Thus, injectable alginate gels offer an attractive platform for local tumor immunotherapy, and facilitate combinatorial treatments designed to promote immune responses locally at a tumor site while limiting systemic exposure to potent immunomodulatory factors.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hori
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stern
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000464:Alginates / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology*; D020100:Hydrogels / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000819:agonists; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000464:Alginates; D019496:Cancer Vaccines; D020100:Hydrogels; D019409:Interleukin-15