2014 Papers - Loo


Enhancement of Antitumor Immunity in a Pulmonary Metastasis Model using Dendritic Cells Loaded with Trp2- Embedded Mesoporous Silica Microparticles

Christopher Loo Surgical Residency Program, University of Hawaii


Background: Recent advances in cancer immunotherapy have generated novel therapies including Provenge, Ipilumab (Yervoy), and Vemurafenib (Zelboraf). We previously demonstrated that nanoparticle-based therapies can be used in a variety of biomedical applications including imaging, integrated cancer imaging/therapy, as well as tissue regeneration. Here we demonstrate a novel dendritic cell-based approach to cancer immunotherapy using Trp2-antigen (melanoma) embedded mesoporous silica microparticles in a B16 pulmonary metastasis model.

Methods: Mesoporous silica microparticle fabrication (MSV): 1 um (diameter) x 400 nm (thickness) discoidal MSV microparticles were fabricated in the Microelectronics Research Center at The University of Texas at Austin by combination of electrochemical etching and standard photolithography. Morphology was verified by scanning electron microscopy (SEM). Tumor inoculation: Using a B16 melanoma pulmonary metastasis model, C57/Bl6 mice were inoculated 10 days prior to treatment. After 10 days, mice in all groups developed pulmonary metastases. N=6 was used in each group for statistical significance. Dendritic cells and antigen loading: DC's were harvested from C57/Bl6 mice. Maturation and purity was measured using FACS analysis. DC's were loaded with MSV, Trp2 alone, or Trp2-loaded MSV. Mice were treated on Day 0. To determine if there was a concentration effect of MSV on treatment efficacy, mice were treated with 0.5, 1.0, and 1.6b MSV. Lungs were harvested 10 days after treatment to assess efficacy.

Results: 100% mortality was observed in untreated mice. Similar results were observed in mice treated with MSV and Trp2 alone. Mortality was attributed to extensive pulmonary metastasis. Enhanced survival was observed in mice treated with dendritic cells loaded with MSV + Trp2. Survival was dose dependent with mice receiving the highest concentration of MSV (1.6b) showing less pulmonary metastasis compared to mice receiving lower doses of MSV (1.0 and 0.5b, respectively).

Discussion: We demonstrate a novel approach to the development of nanoparticle-based dendritic cell therapies using Trp2-embedded mesoporous silica microparticles in a pulmonary metastasis model. We showed an enhanced anti-tumor effect in mice treated with DC's loaded with Trp2-embedded MSV, compared to controls. Mechanistic studies are currently underway. These results have broad applicability in the fields of surgical oncology, cancer immunology, and cancer immunotherapy.