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疾病领域	数量

内分泌与代谢疾病	1
肿瘤	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

CLDN1(Claudin 1)	1

关联

1

项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的药物

Beta-hydroxybutyrate

靶点

CLDN1

作用机制

CLDN1 agonists

在研机构

河北医科大学 [+1]

原研机构

Eppley Institute for Research in Cancer and Allied Diseases

在研适应症

全身炎症反应综合征 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的临床结果

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0 项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的专利（医药）

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925

项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的文献（医药）

2024-09-15·Cancer Research

Abstract B033: MUC16 - Potential Target for Antibody-based Immunotherapy in Pancreatic Cancer

作者: Brooks, Cory L ; Radhakrishnan, Prakash

AbstractPancreatic ductal adenocarcinoma (PDAC) is the most devastating and lethal cancer. PDAC patients with the current standard of care produce dismal overall survival benefits with high toxicities. Thus, there is an unmet clinical need to develop targeted therapeutics against PDAC. Approximately 50 to 70% of PDAC patients overexpress MUC16, which is associated with disease progression, metastasis, drug resistance, and poor patient survival. We demonstrated that MUC16 enhances PDAC tumor growth via binding and activating epidermal growth factor (EGF) receptor family members and its downstream target PI3K/AKT signaling pathways. Here, we show the efficacy of humanized anti-MUC16 antibody (huAR9.6) against MUC16-positive PDAC. Methods: We tested the in vitro efficacy of humanized anti-MUC16 antibody (huAR9.6) against MUC16+ PDAC cells, patient-derived xenografts (PDXs), and patient-derived organoids (PDOs). We evaluated the in vivo therapeutic efficacy of the huAR9.6 antibody in MUC16+ PDAC cells implanted in subcutaneous and orthotopic tumor models. Fucosylated and afucosylated huAR9.6 induced direct tumor-killing activity was evaluated by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with MUC16 positive PDAC cells. Results: Treatment with huAR9.6 reduced the in vitro growth, migration, invasion, and clonogenicity of MUC16+ PDAC cells and patient-derived organoids (PDOs). HuAR9.6 blocked MUC16-mediated ErbB and AKT activation in PDAC, PDOs, and PDX-derived cells. HuAR9.6 treatment induces ADCC and CDC against MUC16+ cells. Removing fucose residue on the N-glycans of the huAR9.6-IgG substantially increased huAR9.6’s ADCC activity. More importantly, huAR9.6 treatment caused PDAC regression in subcutaneous and orthotopic tumor models. Conclusion: The results of this study validate the translational therapeutic potential of huAR9.6 against MUC16-positive PDACs (detected in ∼ 50-70% of patients).Citation Format: Cory L Brooks, Prakash Radhakrishnan. MUC16 - Potential Target for Antibody-based Immunotherapy in Pancreatic Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B033.

2024-05-22·JCI Insight

BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia

Article

作者: Reznicek, Timothy E ; Smith, Audrey L ; Bollag, Gideon ; Vose, Julie M ; Rowley, M Jordan ; El-Gamal, Dalia ; Skupa, Sydney A ; Moore, Dalia Y ; Schmitz, Elizabeth ; Williams, Nolan ; Eiken, Alexandria P ; Bociek, R Gregory ; Kallam, Avyakta ; Powell, Ben ; Mohamed, Eslam ; Mahr, Anna R ; D'Angelo, Christopher R ; Denton, Paul W ; Lunning, Matthew A

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eμ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer inhibitory receptors (IRs) (e.g., PD-1, CD160, CD244, LAG3, VISTA). Complementary results were witnessed in primary CLL cultures, wherein OPN-51107 exerted proinflammatory effects on T cells, regardless of leukemic cell burden. BET-i additionally promotes a progenitor T cell phenotype through reduced expression of transcription factors that maintain terminal differentiation and increased expression of TCF-1, at least in part through altered chromatin accessibility. Moreover, direct T cell effects of BET-i were unmatched by common targeted therapies in CLL. This study demonstrates the immunomodulatory action of BET-i on CLL T cells and supports the inclusion of BET inhibitors in the management of CLL to alleviate terminal T cell dysfunction and potentially enhance tumoricidal T cell activity.

2024-05-01·Nature Cell Biology

Author Correction: Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2–SP1–SAT1 axis

作者: Wang, Dezhen ; Lazenby, Audrey J ; Dasgupta, Aneesha ; Powers, Robert ; Singh, Pankaj K ; Hollingsworth, Michael A ; Ulhannan, Susanna ; Kollala, Sai Sundeep ; Hu, Tuo ; Thakur, Ravi ; Jha, Kanupriya ; Jain, Ajay ; Klinkebiel, David L ; Murthy, Divya ; Souchek, Joshua ; Shukla, Surendra K ; He, Chunbo ; Rana, Sandeep ; Pacheco, Camila ; Grandgenett, Paul M ; Patel, Rohit ; Mehla, Kamiya ; Chaudhary, Sarika ; Rai, Vikant ; Yu, Fang ; Wellen, Kathryn E ; King, Ryan J ; Black, Adrian R ; Kumar, Vikas ; Natarajan, Amarnath ; Mulder, Scott E ; Edil, Barish H ; Gebregiworgis, Teklab ; Chaika, Nina V ; Attri, Kuldeep S ; Ly, Quan ; Hwang, Rosa F

100 项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的药物交易

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100 项与 Eppley Institute for Research in Cancer and Allied Diseases 相关的转化医学

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