Increased immunogenicity of a minimally immunogenic tumor after cancer-targeting near infrared photoimmunotherapy

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

研究成果: ジャーナルへの寄稿学術誌査読

25 被引用数 (Scopus)

抄録

Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer treatment that employs an antibody photoabsorber conjugate (APC) composed of a targeting monoclonal antibody (mAb) conjugated with a photoactivatable phthalocyanine-derivative dye. Once injected and allowed to bind to a tumor, the APC is activated by local near-infrared light which kills cancer cells and induces a strong immune response in the tumor microenvironment by unmasking of new tumor antigens emerging from damaged tumor cells. Due to its ability to incite an immune reaction, even in poorly immunogenic tumors, NIR-PIT has the potential to enhance immunogenicity in tumors especially after immune checkpoint inhibition. In this study, we employ a poorly immunogenic MOC2-luc syngeneic tumor model and evaluate the efficacy of cancer-targeting CD44-targeted NIR-PIT. Increased infiltration of CD8+ T cells observed after NIR-PIT suggested an enhanced immune environment. Next, we evaluated tumor progression and survival after the combination of CD44-targeted NIR-PIT and short-term administration of an anti-PD1 immune checkpoint inhibitor (ICI) to further activate CD8+ T cells. Additionally, in mice in which the tumors were eradicated by this combination therapy, a re-challenge with fresh MOC2-luc cells demonstrated failure of tumor implantation implying acquired long-term immunity against the cancer cells. Combination therapy decreased tumor progression and prolonged survival significantly. Therefore, we concluded that NIR-PIT was able to convert a minimally immunogenic tumor unresponsive to anti-PD-1 ICI into a highly immunogenic tumor responsive to anti-PD-1 ICI, and this therapy was capable of inducing long-term immunity against the treated cancer.

本文言語英語
論文番号3747
ページ(範囲)1-15
ページ数15
ジャーナルCancers
12
12
DOI
出版ステータス出版済み - 12月 2020

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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