DTIC ADA540718: Second Generation Therapeutic DNA Lymphoma pdf

DTIC ADA540718: Second Generation Therapeutic DNA Lymphoma

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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

• Creator/s: Defense Technical Information Center
• Date: 5/1/2010
• Year: 2010
• Book Topics/Themes: DTIC Archive, , M D ANDERSON CANCER CENTER HOUSTON TX, *VACCINES, *DEOXYRIBONUCLEIC ACIDS, *LYMPHOMAS, T LYMPHOCYTES, ANTIGENS, RECEPTOR SITES(PHYSIOLOGY), LIGANDS, NEOPLASMS, PROTEINS, TABLES(DATA

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