Interleukin-15 after near-infrared photoimmunotherapy (Nir-pit) enhances t cell response against syngeneic mouse tumors

Yasuhiro Maruoka, Aki Furusawa, Ryuhei Okada, Fuyuki Inagaki, Hiroaki Wakiyama, Takuya Kato, Tadanobu Nagaya, Peter L. Choyke, Hisataka Kobayashi

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by 690 nm light. Cancer cell-targeted NIR-PIT induces rapid necrotic/immunogenic cell death (ICD) that induces antitumor host immunity including re-priming and proliferation of T cells. Interleukin-15 (IL-15) is a cytokine that activates natural killer (NK)-, B-and T-cells while having minimal effect on regulatory T cells (Tregs) that lack the IL-15 receptor. Here, we hypothesized that IL-15 administration with cancer cell-targeted NIR-PIT could further inhibit tumor growth by increasing antitumor host immunity. Three syngeneic mouse tumor models, MC38-luc, LL/2, and MOC1, underwent combined CD44-targeted NIR-PIT and short-term IL-15 administration with appropriate controls. Comparing with the single-agent therapy, the combination therapy of IL-15 after NIR-PIT inhibited tumor growth, prolonged survival, and increased tumor infiltrating CD8+ T cells more efficiently in tumor-bearing mice. IL-15 appears to enhance the therapeutic effect of cancer-targeted NIR-PIT.

Original languageEnglish
Article number2575
Pages (from-to)1-13
Number of pages13
JournalCancers
Volume12
Issue number9
DOIs
Publication statusPublished - Sept 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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