Using an adoptive transfer model, Leleux et al. showed that priming with a non-integrating, DC- targeted lentiviral vector (ZVexTM) expanded a durable antigen-specific CD8+ T cell response. Greater, durable secondary responses, marked by increased CD8+ T cells making IFNγ and sometimes IL-2 and TNF, were attained by heterologous versus homologous boosting with antigen in an adenovector, or adjuvanted with a TLR4 agonist or self-replicating RNA nanoparticles. Antigen boosting with ZVex was ineffective regardless of priming strategy. A ZVex-initiated heterologous regimen increased antitumor murine responses and generated antigen-specific memory T cells.
Contributed by Paula Hochman
ABSTRACT: Therapeutic cancer vaccines must induce high levels of tumor-specific cytotoxic CD8 T cells to be effective. We show here that tumor-antigen specific effector and memory T cell responses primed with a non-integrating, dendritic-cell targeted lentiviral vector (ZVexTM) could be boosted significantly by either adjuvanted recombinant protein, adenoviral vectors, or self-replicating RNA. These heterologous prime-boost regimens also provided significantly better protection in murine tumor models. In contrast, homologous prime-boost regimens, or using the lentiviral vector as a boost, resulted in lower T cell responses with limited therapeutic efficacy. Heterologous prime-boost regimens that utilize ZVex as the prime may be attractive modalities for therapeutic cancer vaccines.
Author Info: (1) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: jardin.leleux@gmail.com. (2) Immune Design Corp., Sea
Author Info: (1) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: jardin.leleux@gmail.com. (2) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. (3) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. (4) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. (5) Immune Design Corp., Seattle, WA, A Wholly Owned Subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
