Author: Hristopoulos, Maria ; Laing, Steven T. ; Lee, Genee ; Totpal, Klara ; Polson, Andrew G. ; Prell, Rodney A. ; Sukumaran, Siddharth ; Zhang, Crystal ; Lin, Kedan ; Tam, Lucinda ; Mathieu, Mary ; Dennis, Mark S. ; Vuillemenot, Brian R. ; Stainton, Shannon ; Gu, Chen ; Nguyen, Allen ; Newman, Robert ; Ellerman, Diego ; Lu, Elizabeth ; Leong, Steven R. ; Zheng, Bing ; Wong, Alfred ; Chu, Yu-Waye

Key PointsBispecific antibodies binding CD3 and CLL-1 deplete CLL-1+ target cells in animal models. An appropriately engineered CLL-1/CD3 bispecific antibody could be effective in treating AML.

01 May 2008·Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology

[The role of extracellular domain of human 4-1BBL in regulating activities of human peripheral blood lymphocytes in vitro].

Article

Author: Xu, Yuan-fu ; Fan, Dong-mei ; Yang, Chun-zheng ; Shao, Xiao-feng ; Su, Ye ; Cheng, Xin ; Xiong, Dong-sheng ; Guo, Hong-xing

AIMTo investigate the role of the extracellular domain of human 4-1BBL (ex4-1BBL) in regulating the in vitro activities of peripheral blood lymphocytes (PBL).METHODSViable cells were quantified with Trypan-blue exclusion assay. CytoTox 96 Nonradioactive Cytotoxicity Assay Kit was used for measuring LDH levels of supernatant. ELISA kit was used for measuring IL-2 level. In vitro cytotoxity of PBL combined with anti-CD3/anti-Pgp bispecific diabody plus ex4-1BBL was analyzed with CytoTox 96 nonradioactive method.RESULTSEx4-1BBL can increase the proliferation of PBL, reduce cell death, promote IL-2 secretion, and the experimental group with ex4-1BBL showed obviously enhanced cytotoxic effect toward K562/A02 cells.CONCLUSIONEx4-1BBL may be an important adjuvant for improving activities of PBL.

01 Jan 2008·Cellular ImmunologyQ3 · MEDICINE

Extracellular domain of 4-1BBL enhanced the antitumoral efficacy of peripheral blood lymphocytes mediated by anti-CD3×anti-Pgp bispecific diabody against human multidrug-resistant leukemia

Q3 · MEDICINE

Article

Author: Xin Cheng ; Wenguo Jiang ; Wenge Liu ; Ming Yang ; Hongxing Guo ; Dongsheng Xiong ; Chunzheng Yang ; Yuan Zhou ; Jing Qi ; Zhenping Zhu ; Yingdai Gao ; Jinhong Wang

Our previous data have shown a significantly higher tumor response to anti-CD3/anti-Pgp bispecific diabody-mediated immunotherapy for P-glycoprotein (Pgp)-overexpressing K562/A02 cells, but a rapid tumor relapse occurred at 1 week after therapy. In an attempt to overcome tumor recurrence, we supplemented the previous therapy with extracellular domain of human 4-1BBL (ex4-1BBL) to regulate the activation of peripheral blood lymphocyte (PBL). As a result, this combination showed enhanced cytotoxicity in vitro and eradicated the multidrug-resistant xenografts of K562/A02 in nude mice. Furthermore, no tumor recurrence was observed within 100 days after the first treatment. Therefore, when used as an adjuvant, ex4-1BBL may improve the outcome of PBL-based immunotherapy.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	IND Approval	CN	Excelmab, Inc.	15 Mar 2023
Pancreatic Cancer	Preclinical	CN	Excelmab, Inc.	30 Jan 2022
Pancreatic Cancer	Preclinical	US	Excelmab, Inc.	30 Jan 2022

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