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KAIST 의과학대학원

EBioMedicine, Mar 19 2026, 126 S2352-3964(26)00098-8 | https://doi.org/10.1016/j.ebiom.2026.106216 The therapeutic effects of the VEGF decoy receptor fusion protein VEGF-Grab in chronic inflammatory diseases

Youngeun Lee ^{a j}, Hee-Young Lee ^{b c j}, Hye Seong Lim ^d, Jin A. Shin ^d, Hyun Gul Yang ^d, Saseong Lee ^b, Grazia Mercadante ^e, Valeria Cicatiello ^e, Sandro De Falco ^e, Hyungmin Kim ^f, Chaerin Kim g, Su-Hyun Lee^{f g}, Yu-Mi Kim^{b c}, Seung-Ah Yoo ^{b c}, Seung-Hyo Lee ^{a h}, Wan-Uk Kim ^{b i *}

^aGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
^bCenter for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea
^cDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea
^dPanolos Bioscience, Inc., Hwaseong-si, Republic of Korea
^eIstituto di Genetica e Biofisica Adriano Buzzati-Traverso, National Research Council, Napoli, Italy
^fPostech-Catholic Biomedical Engineering Institute, Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea
^gDepartment of Medical Sciences, Graduate School of the Catholic University of Korea, Seoul, Republic of Korea
^hDepartment of Biomedical Science, College of Medicine, Korea University, Seoul, Republic of Korea
ⁱDivision of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea

^*Corresponding authors: correspondence to Seung-Ah Yoo, Seung-Hyo Lee or Wan-Uk Kim

Abstract

Background
Placental growth factor (PlGF) plays a crucial role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA) and multiple sclerosis (MS), by enhancing angiogenesis, disease-aggravating features of fibroblast-like synoviocytes (FLSs), and pathogenic T helper type 17 (Th17) cells. The therapeutic potential of a VEGF decoy receptor fusion protein, VEGF-Grab, which potently binds and neutralises VEGF and PlGF, has not been studied in autoimmune diseases. Therefore, we investigated the therapeutic effects of VEGF-Grab in RA and MS by using in vitro and in vivo models.

Methods
Two forms of VEGF-Grab (PB101 and PB102) were engineered to enhance their binding affinity for VEGF and PlGF. In vitro assays-including Transwell migration and wound-healing assays of endothelial cells and FLSs, as well as Th17 cell differentiation-were employed to evaluate the effects of VEGF-Grab on angiogenesis and immune-cell function. To assess therapeutic efficacy in vivo, mouse models of inflammatory and autoimmune arthritis, as well as experimental autoimmune encephalomyelitis (EAE), were utilised.

Findings
Our results indicate that VEGF-Grab exerted significant inhibitory effects across various animal models of autoimmune diseases, targeting abnormal angiogenesis, cartilage invasion, and pathogenic Th17 cells. Furthermore, combined treatment with IFN-β in the EAE model suggested enhanced efficacy of therapeutic effects.

Interpretation
Our findings highlight the multifaceted therapeutic potential of VEGF-Grab in RA and MS, targeting angiogenesis, the aggressiveness of FLSs, and the pathogenicity of Th17 cells, all driven by the ‘angio-lymphokine’, PlGF. Thus, VEGF-Grab has the potential to be a therapeutic candidate for the treatment of RA and MS, warranting further clinical exploration.

논문정보

형식Research article
게재일2026년 03월 (BRIC 등록일 2026-03-26)
연구진국내 연구진
분야 의약학 > 면역의학

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