Combined CD44- And CD25-targeted near-infrared photoimmunotherapy selectively kills cancer and regulatory T cells in syngeneic mouse cancer models

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

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a mAb conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is a surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, CD25- targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3+ CD25+ CD4+ regulatory T cells (Treg), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44- and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removing FOXP3+ CD25+ CD4+ Tregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44- and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44- and CD25-targeted NIR-PIT also resulted in some complete remissions. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.

Original languageEnglish
Pages (from-to)345-355
Number of pages11
JournalCancer Immunology Research
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Combined CD44- And CD25-targeted near-infrared photoimmunotherapy selectively kills cancer and regulatory T cells in syngeneic mouse cancer models'. Together they form a unique fingerprint.

Cite this