A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis

Ayako Nishimoto, Izumi Sato, Kiyotaka Nakano, Hiroshi Ohmori, Yoko Kayukawa, Kayukawa Y, Tanimura H, Hiromi Tanimura, Sachiya Yamamoto, Yuichiro Sakamoto, Sakamoto Y, Genki Nakamura, Nakamura G, Atsuhiko Maeda, Maeda A, Kentaro Asanuma, Kato A, Atsuhiko Kato, Tadashi Sankai, Ryo Konno, Yamada-Okabe H, Hisafumi Yamada‐Okabe, Hisafumi Yamada-Okabe
Science translational medicine · 2023 · vol. 15(684) , pp. eabq5858 · doi:10.1126/scitranslmed.abq5858 · PMID:36812343 · W4321481029
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A long-acting anti-IL-8 antibody (AMY109) reduced endometriotic lesion volume, disease severity, fibrosis, and adhesions in a monkey model by inhibiting neutrophil recruitment and monocyte chemoattractant protein-1 production.

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Abstract

Current pharmacological treatments for endometriosis are limited to hormonal agents that can relieve pain but cannot cure the disease. Therefore, the development of a disease-modifying drug for endometriosis is an unmet medical need. By studying human endometriotic samples, we found that the progression of endometriosis was associated with the development of inflammation and fibrosis. In addition, IL-8 expression was highly up-regulated in endometriotic tissues and closely correlated with disease progression. We created a long-acting recycling antibody against IL-8 (AMY109) and evaluated its clinical potency. Because rodents do not produce IL-8 and do not experience menstruation, we analyzed the lesions in cynomolgus monkeys that spontaneously developed endometriosis and in a surgically induced endometriosis monkey model. Both spontaneously developed and surgically induced endometriotic lesions demonstrated pathophysiology that was highly similar to that of human endometriosis. Once-a-month subcutaneous injection of AMY109 to monkeys with surgically induced endometriosis reduced the volume of nodular lesions, lowered the Revised American Society for Reproductive Medicine score as modified for monkeys, and ameliorated fibrosis and adhesions. In addition, experiments using cells derived from human endometriosis revealed that AMY109 inhibited the recruitment of neutrophils to endometriotic lesions and the production of monocyte chemoattractant protein-1 from neutrophils. Thus, AMY109 may represent a disease-modifying therapy for patients with endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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