Immunoregulation by IL-7R-targeting antibody-drug conjugates: Overcoming steroid-resistance in cancer and autoimmune disease

Masahiro Yasunaga, Shino Manabe, Yasuhiro Matsumura

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Steroid-resistance is a common complication in the treatment of malignancies and autoimmune diseases. IL-7/IL-7R signaling, which regulates lymphocyte growth and survival, has been implicated in the development of malignancies and autoimmune diseases. However, the biological significance of IL-7/IL-7R signaling in steroid treatment is poorly understood. Here, we identified a novel relationship between IL-7R signaling and steroid-resistance, and showed that an anti-IL-7R antibody conjugated with SN-38 (A7R-ADC-SN-38) has strong anti-tumor effects against both parental and steroid-resistant malignant cells. Furthermore, inflammation in the mouse autoimmune arthritis model was suppressed to greater extent by A7R-ADC conjugated to MMAE than by A7R-ADC-SN-38. Given that an increased proportion of IL-7R-positive cells is a common mechanism underlying the pathogenesis of autoimmunity, we found that specific depletion of this cell population abrogated the progression of disease. This suggests that the cytotoxicity and immunosuppressive capacity of A7R-ADC could be modulated to treat specific malignancies or autoimmune diseases through the introduction of different payloads, and represents a novel alternative to steroid therapy.

Original languageEnglish
Article number10735
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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