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Engineered CCR5 superagonist chemokine as adjuvant in anti-tumor DNA vaccination
Karim Dorgham1, Valérie Abadie, Mutsunori Iga
1Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Paris, France.
Abstract:
Chemokine receptors are promising targets for enhancing T-cell immunity and anti-cancer therapy. CCL5 is a potential adjuvant for DNA vaccination. We postulated that CCR5 superagonists could be even more effective. A CCR5 superagonist derived from natural CCL5 by directed in vitro evolution, namely 1P7, is used as a DNA vaccine adjuvant and expressed as fused chemokine-Ig (1P7-Ig). We show that OVA+1P7-Ig DNA co-inoculation induced higher frequencies of OVA-specific CD8 lymphocytes than OVA+CCL5-Ig or controls and gave an even better protection against tumor growth in a CCR5-dependant manner. Our results indicate that CCR5-superagonists may provide potent adjuvants for vaccines.
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