Open AccessA DNA-Launched Nanoparticle Vaccine Elicits CD8+ T-cell Immunity to Promote In Vivo Tumor Control
Author(s) -
Ziyang Xu,
Neethu Chokkalingam,
Edgar TelloRuiz,
Megan C. Wise,
M. Bah,
Susanne Walker,
Nicholas J. Tursi,
Paul D. Fisher,
Katherine Schultheis,
Kate E. Broderick,
Laurent Humeau,
Daniel W. Kulp,
David B. Weiner
Publication year - 2020
Publication title -
cancer immunology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.976
H-Index - 87
eISSN - 2326-6074
pISSN - 2326-6066
DOI - 10.1158/2326-6066.cir-20-0061
Subject(s) - ctl* , dna vaccination , cytotoxic t cell , epitope , cancer vaccine , electroporation , cd8 , biology , immunology , vaccination , cancer immunotherapy , immune system , immunotherapy , virology , cancer research , antigen , immunization , in vitro , biochemistry , gene
Cytolytic T cells (CTL) play a pivotal role in surveillance against tumors. Induction of CTL responses by vaccination may be challenging, as it requires direct transduction of target cells or special adjuvants to promote cross-presentation. Here, we observed induction of robust CTL responses through electroporation-facilitated, DNA-launched nanoparticle vaccination (DLnano-vaccines). Electroporation was observed to mediate transient tissue apoptosis and macrophage infiltration, which were deemed essential to the induction of CTLs by DLnano-vaccines through a systemic macrophage depletion study. Bolus delivery of protein nano-vaccines followed by electroporation, however, failed to induce CTLs, suggesting direct in vivo production of nano-vaccines may be required. Following these observations, new DLnano-vaccines scaffolding immunodominant melanoma Gp100 and Trp2 epitopes were designed and shown to induce more potent and consistent epitope-specific CTL responses than the corresponding DNA monomeric vaccines or CpG-adjuvanted peptide vaccines. DNA, but not recombinant protein, nano-vaccinations induced CTL responses to these epitopes and suppressed melanoma tumor growth in mouse models in a CD8 + T-cell-dependent fashion. Further studies to explore the use of DLnano-vaccines against other cancer targets and the biology with which they induce CTLs are important.