Selective blockade of latent TGF-β1 activation suppresses tissue fibrosis with good safety

  • Commun Med (Lond). 2026 Jan 28;6(1):131. doi: 10.1038/s43856-026-01408-w.
Masakazu Kanamori  #  1 ,  Izumi Sato  #  1 ,  Christine Xing'er Koo  2  3 ,  Yang Sun  2 ,  Hiroki Kawauchi  1 ,  Kenji Nakagawa  1 ,  Atsuko Murai  4 ,  Kentaro Asanuma  4 ,  Siok Wan Gan  2 ,  Chai Ling Pang  2  5 ,  Yuichiro Shimizu  1 ,  Meiri Shida-Kawazoe  1 ,  Chisako Kanamaru  4 ,  Yoko Kayukawa  1 ,  Natsuko Hada  1 ,  Ken Ohmine  4 ,  Takehisa Kitazawa  1 ,  Junichi Nezu  1  6 ,  Tomoyuki Igawa  1 ,  Hideaki Shimada  7  8
Affiliations
  • 1. Research Division, Chugai Pharmaceutical Co. Ltd., Yokohama, Kanagawa, Japan.
  • 2. Chugai Pharmabody Research Pte. Ltd., Singapore, Singapore.
  • 3. Health Sciences Authority, Singapore, Singapore.
  • 4. Translational Research Division, Chugai Pharmaceutical Co. Ltd., Yokohama, Kanagawa, Japan.
  • 5. AbbVie Operations Singapore Pte. Ltd., Singapore, Singapore.
  • 6. Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
  • 7. Research Division, Chugai Pharmaceutical Co. Ltd., Yokohama, Kanagawa, Japan. [email protected].
  • 8. Chugai Pharmabody Research Pte. Ltd., Singapore, Singapore. [email protected].
  • # Contributed equally.
PMID: 41606188 DOI: 10.1038/s43856-026-01408-w
Abstract

Background: Fibrosis is a hallmark of organ failure observed after chronic epithelial injury and inflammation. The transforming growth factor beta (TGF-β) is the master regulator of fibrogenesis, so blockade of the TGF-β pathway is a potential treatment strategy for fibrosis; however, the therapeutic potential of pan-TGF-β blockade is limited by side effects.

Methods: We generated SOF10, a humanized antibody that targets latent TGF-β1 and selectively blocks protease- and Integrin αvβ8-mediated latent TGF-β1 activation. We conducted gene expression and histological analyses in nonalcoholic steatohepatitis (NASH)/liver fibrosis and renal interstitial fibrosis models. We also evaluated the combination effect of SOF10 with an immune checkpoint inhibitor in a syngeneic mouse model and performed safety studies in mice and monkeys.

Results: Here we show that SOF10 reduces fibrosis in NASH/liver fibrosis and renal interstitial fibrosis models and improves renal function in a chronic kidney disease model. Furthermore, the combination of SOF10 with an anti-PD-L1 antibody decreases tumor growth in a syngeneic mouse model. SOF10 demonstrates safety in both mice and monkeys.

Conclusions: Selective blockade of latent TGF-β1 activation represents a promising approach for treating a broad range of fibrotic diseases and cancers. By specifically targeting TGF-β1, SOF10 may offer a safer and more effective therapeutic option compared to non-selective TGF-β inhibitors. This strategy has the potential to transform the treatment paradigm for fibrosis-related conditions.