Rapid expansion of highly functional antigen-specific t cells from patients with melanoma by nanoscale artificial antigen-presenting cells

Junya Ichikawa, Tatsuya Yoshida, Ariel Isser, Andressa S. Laino, Melinda Vassallo, David Woods, Sojung Kim, Mathias Oelke, Kristi Jones, Jonathan P. Schneck, Jeffrey S. Weber

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose: Generation of antigen-specific T cells from patients with cancer employs large numbers of peripheral blood cells and/or tumor-infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of restimulation ex vivo. We used a novel paramagnetic, nanoparticle-based artificial antigen-presenting cell (nano-aAPC) that combines anti-CD28 costimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen-specific T cells from patients with melanoma. Experimental Design: Nano-aAPC-expressing HLA-A*0201 molecules and costimulatory anti-CD28 antibody and HLA-A*0201 molecules loaded with MART-1 or gp100 class I-restricted peptides were used to stimulate CD8 T cells purified from the peripheral blood of treatment-na€1ve or PD-1 antibody-treated patients with stage IV melanoma. Expanded cells were restimulated with fresh peptide-pulsed nano-aAPC at day 7. Phenotype analysis and functional assays including cytokine release, cytolysis, and measurement of avidity were conducted. Results: MART-1-specific CD8 T cells rapidly expanded up to 1,000-fold by day 14 after exposure to peptide-pulsed nano-aAPC. Expanded T cells had a predominantly stem cell memory CD45RAþ/CD62Lþ/CD95þ phenotype; expressed ICOS, PD-1, Tim3, and LAG3; and lacked CD28. Cells from patients with melanoma were polyfunctional; highly avid; expressed IL2, IFNg, and TNFa; and exhibited cytolytic activity against tumor cell lines. They expanded 2- to 3-fold after exposure to PD-1 antibody in vivo, and expressed a highly diverse T-cell receptor V beta repertoire. Conclusions: Peptide-pulsed nano-aAPC rapidly expanded polyfunctional antigen-specific CD8 T cells with high avidity, potent lytic function, and a stem cell memory phenotype from patients with melanoma.

Original languageEnglish (US)
Pages (from-to)3384-3396
Number of pages13
JournalClinical Cancer Research
Issue number13
StatePublished - Jul 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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