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A Phase 1 Single and Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 in Healthy Volunteers and Idiopathic Pulmonary Fibrosis Subjects

This is a first-in-human, two-part, Phase 1 study that will characterize the safety, tolerability, PK, and immunogenicity of HuL001.

开始日期2021-08-31

申办/合作机构

上毅生物科技股份有限公司

100 项与上毅生物科技股份有限公司相关的临床结果

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0 项与上毅生物科技股份有限公司相关的专利（医药）

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4

项与上毅生物科技股份有限公司相关的文献（医药）

2023-11-01·Oncology reports

Unrevealed roles of extracellular enolase‑1 (ENO1) in promoting glycolysis and pro‑cancer activities in multiple myeloma via hypoxia‑inducible factor 1α.

Article

作者: Wu, Pei-Yu ; Huang, Yung-Tsang ; Huang, Wei-Ching ; Chung, I-Che ; Tsai, An-Wei ; Yuan, Ta-Tung ; Chen, Mao-Lin

The involvement of enolase‑1 (ENO1), intracellularly or extracellularly, has been implicated in cancer development. Moreover, anticancer activities of an ENO1‑targeting antibody has demonstrated the pathological roles of extracellular ENO1 (surface or secreted forms). However, although ENO1 was first identified as a glycolytic enzyme in the cytosol, to the best of our knowledge, extracellular ENO1 has not been implicated in glycolysis thus far. In the present study, the effects of extracellular ENO1 on glycolysis and other related pro‑cancer activities were investigated in multiple myeloma (MM) cells in vitro and in vivo. Knockdown of ENO1 expression reduced lactate production, cell viability, cell migration and surface ENO1 expression in MM cells. Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxia‑inducible factor 1‑α (HIF‑1α) expression, glycolysis‑related gene (GRG) expression and pro‑cancer activities, such as cell migration, cell viability and tumor‑promoting cytokine secretion. Consistently, these extracellular ENO1‑induced cellular effects were inhibited by an ENO1‑specific monoclonal antibody (mAb). In addition, extracellular ENO1‑mediated glycolysis, GRG expression and pro‑cancer activities were also reduced by HIF‑1α silencing. Lastly, administration of an ENO1 mAb reduced tumor growth and serum lactate levels in an MM xenograft model. These results suggested that extracellular ENO1 (surface or secreted forms) enhanced a HIF‑1α‑mediated glycolytic pathway, in addition to its already identified roles. Therefore, the results of the present study highlighted the therapeutic potential of ENO1‑specific antibodies in treating MM, possibly via glycolysis inhibition, and warrant further studies in other types of cancer.

2022-08-02·Molecular Cancer Therapeutics

A Novel Enolase-1 Antibody Targets Multiple Interacting Players in the Tumor Microenvironment of Advanced Prostate Cancer

Article

作者: Chung, I-Che ; Yuan, Ta-Tung ; Huang, Wei-Ching ; Huang, Yung-Tsang ; Chuang, Chi-Fen ; Chen, Mao-Lin

AbstractProstate cancer is one of the most common causes of cancer death in men worldwide, and the treatment options are limited for patients with advanced stages of prostate cancer. Upon oncogenic or inflammatory stimulation, tumor cells or immune cells express cell surface enolase-1 (ENO1) as plasminogen receptor to facilitate their migration via plasmin activation. Little is known about the roles of ENO1 in prostate cancer, especially in the tumor microenvironment (TME). We hypothesized that targeting surface ENO1 with specific mAbs would exert multifactorial therapeutic potentials against prostate cancer. In vivo, we showed ENO1 mAb (HuL227) reduced the growth of subcutaneous PC-3 xenograft, monocytes recruitment, and intratumoral angiogenesis. In a PC-3 intratibial implantation model, HuL227 reduced tumor growth and osteoclast activation in the bone. To investigate the antitumor mechanism of ENO1 mAb, we found that blocking surface ENO1 significantly reduced VEGF-A–induced tube formation of endothelial cells in vitro. Furthermore, HuL227 inhibited inflammation-enhanced osteoclasts activity and the secretion of invasion-related cytokines CCL2 and TGFβ from osteoclasts. In addition, inflammation-induced migration and chemotaxis of androgen-independent prostate cancer cells were dose-dependently inhibited by HuL227. In summary, we showed that, ENO1 mAb targets multiple TME niches involved in prostate cancer progression and bone metastasis via a plasmin-related mechanism, which may provide a novel immunotherapy approach for men with advanced prostate cancer.

Oncology Reports

Unrevealed roles of extracellular enolase-1 (ENO1) in promoting glycolysis and pro-cancer activities in multiple myeloma via hypoxia-inducible factor 1alpha

作者: Huang, Yung-Tsang ; Wu, Pei-Yu ; Huang, Wei-Ching ; Chung, I-Che ; Tsai, An-Wei ; Yuan, Ta-Tung ; Chen, Mao-Lin

The involvement of enolase-1 (ENO1), intracellularly or extracellularly, has been implicated in cancer development.Moreover, anticancer activities of an ENO1 targeting antibody has demonstrated the pathol. roles of extracellular ENO1 (surface or secreted forms).However, although ENO1 was first identified as a glycolytic enzyme in the cytosol, to the best of our knowledge, extracellular ENO1 has not been implicated in glycolysis thus far.In the present study, the effects of extracellular ENO1 on glycolysis and other related pro-cancer activities were investigated in multiple myeloma (MM) cells in vitro and in vivo.Knockdown of ENO1 expression reduced lactate production, cell viability, cell migration and surface ENO1 expression in MM cells.Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxia-inducible factor 1-alpha (HIF-1alpha ) expression, glycolysis-related gene (GRG) expression and pro-cancer activities, such as cell migration, cell viability and tumor-promoting cytokine secretion.Consistently, these extracellular ENO1-induced cellular effects were inhibited by an ENO1 specific monoclonal antibody (mAb).In addition, extracellular ENO1-mediated glycolysis, GRG expression and pro-cancer activities were also reduced by HIF-1alpha silencing.Lastly, administration of an ENO1 mAb reduced tumor growth and serum lactate levels in an MM xenograft model.These results suggested that extracellular ENO1 (surface or secreted forms) enhanced a HIF-1alpha -mediated glycolytic pathway, in addition to its already identified roles.Therefore, the results of the present study highlighted the therapeutic potential of ENO1-specific antibodies in treating MM, possibly via glycolysis inhibition, and warrant further studies in other types of cancer.

100 项与上毅生物科技股份有限公司相关的药物交易

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100 项与上毅生物科技股份有限公司相关的转化医学

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