Second Generation Therapeutic DNA Lymphoma Vaccines
Abstract
Our laboratory previously described the strategy of fusing chemokine receptor ligands to antigens in order to generate immunogenic DNA vaccines. In the present study, among a panel of chemokine receptor ligands tested, murine Beta-defensin2 (mBD2) was superior in inducing resistance to B16 melanoma when fused to gp100. We produced corresponding fusion proteins using both ovalbumin (OVA) and gp100 as model antigens. Superior cross-presentation by dendritic cells (DC) was observed for mBD2 fused antigens over unfused antigens in vitro. In vivo, we observed significant increases in the expansion of adoptively transferred antigen specific MHC class I, but not class II-restricted T cells after immunization with mBD2 fused OVA over OVA alone. This enhanced expansion of class I restricted T cells was Toll-like receptor 4 (TLR4) dependent, but CC chemokine receptor 6 (CCR6) independent. Superior tumor resistance was observed for mBD2-fusion protein vaccines, compared with unfused antigen, in both tumor models. These data suggest that production of mBD2 fusion protein vaccines are feasible and that they induce anti-tumor immunity, through a mechanism of TLR4-mediated uptake or uptake by an as yet unidentified receptor on DC.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA540718
Entities
People
- Larry Kwak
Organizations
- The University of Texas MD Anderson Cancer Center