| First Author | Gehrmann U | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 13 | Pages | 3865-76 |
| PubMed ID | 23658368 | Mgi Jnum | J:199010 |
| Mgi Id | MGI:5500108 | Doi | 10.1158/0008-5472.CAN-12-3918 |
| Citation | Gehrmann U, et al. (2013) Synergistic Induction of Adaptive Antitumor Immunity by Codelivery of Antigen with alpha-Galactosylceramide on Exosomes. Cancer Res 73(13):3865-76 |
| abstractText | Exosomes and the invariant NKT (iNKT) immune cell ligand alpha-galactosylceramide (alphaGC) may offer novel tools for cancer immunotherapy. In this study, we investigated whether exosomes loaded with alphaGC can activate iNKT cells and potentiate a cancer-specific adaptive immune response. alphaGC loaded exosomes readily activated iNKT cells both in vitro and in vivo. Exosomes loaded with alphaGC plus the model antigen ovalbumin (OVA) induced potent NK and gammadelta T-cell innate immune responses, and they also synergistically amplified T- and B-cell responses that were OVA specific. In contrast to soluble alphaGC, which anergizes iNKT cells, we found that alphaGC/OVA-loaded exosomes did not induce iNKT cell anergy but were more potent than soluble alphaGC + OVA in inducing adaptive immune responses. In an OVA-expressing mouse model of melanoma, treatment of tumor-bearing mice with alphaGC/OVA-loaded exosomes decreased tumor growth, increased antigen-specific CD8(+) T-cell tumor infiltration, and increased median survival, relative to control mice immunized with soluble alphaGC + OVA alone. Notably, an additional injection of alphaGC/OVA-loaded exosomes further augmented the treatment effects. Our findings show that exosomes loaded with protein antigen and alphaGC will activate adaptive immunity in the absence of triggering iNKT-cell anergy, supporting their application in the design of a broad variety of cancer immunotherapy trials. Cancer Res; 73(13); 3865-76. (c)2013 AACR. |
