scholarly journals An antibody-tumor necrosis factor fusion protein that synergizes with oxaliplatin for treatment of colorectal cancer

2019 ◽  
Author(s):  
Davor Bajic ◽  
Kerry A. Chester ◽  
Dario Neri
Keyword(s):  
Colorectal Cancer ◽  
Tumor Necrosis Factor ◽  
Fusion Protein ◽  
Mammalian Cells ◽  
Tumor Necrosis ◽  
Human Antibody ◽  
Single Chain ◽  
Single Chain Fv ◽  
Immunocompetent Mice ◽  
Necrosis Factor

ABSTRACTWe have cloned and characterized a novel fusion protein (Sm3E-TNF), consisting of the monoclonal antibody Sm3E in single-chain Fv fragment format, fused to murine tumor necrosis factor. The protein, which was expressed in mammalian cells and purified as a non-covalent stable homotrimer, bound to the cognate carcinoembryonic antigen (CEA) and retained tumor necrosis factor activity. A quantitative biodistribution experiment, performed in immunocompetent mice with CT26 colon carcinomas transfected with human CEA, revealed that Sm3E-TNF was able to preferentially accumulate in the tumors with excellent selectivity (tumor:blood ratio = 56:1, twenty-four hours after intravenous administration). The fusion protein mediated a rapid hemorrhagic necrosis of a large portion of the tumor mass, but a rim survived and eventually regrew. Surprisingly, the combination of Sm3E-TNF with 5-fluorouracil led to a reduction of therapeutic activity, while a combination with oxaliplatin led to a prolonged stabilization, with complete tumor eradication in 40% of treated mice. These therapy results were confirmed in a second immunocompetent mouse model of colorectal cancer (CEA-transfected C51 tumors) and provide a rationale for the possible clinical use of oxaliplatin in combination with fully-human antibody-TNF fusions.

In Vivo Tumor Delivery of a Recombinant Single-Chain Fv::Tumor Necrosis Factor:  A Fusion Protein

2002 ◽  
Vol 13 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Stephen P. Cooke ◽  
R. Barbara Pedley ◽  
R. Boden ◽  
Richard H. J. Begent ◽  
Kerry A. Chester
Keyword(s):  
Tumor Necrosis Factor ◽  
Fusion Protein ◽  
Tumor Necrosis ◽  
Single Chain ◽  
Single Chain Fv ◽  
Tumor Delivery ◽  
Necrosis Factor

scholarly journals In Vivo Tumor Delivery of a Recombinant Single Chain Fv::Tumor Necrosis Factor-α Fusion Protein

2002 ◽  
Vol 13 (2) ◽  
pp. 385-385 ◽  
Author(s):  
Stephen P. Cooke ◽  
R. Barbara Pedley ◽  
R. Boden ◽  
Richard H. J. Begent ◽  
Kerry A. Chester
Keyword(s):  
Tumor Necrosis Factor ◽  
Fusion Protein ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Single Chain ◽  
Single Chain Fv ◽  
Tumor Delivery ◽  
Factor Α ◽  
Necrosis Factor

Production of recombinant tumor necrosis factor receptor/Fc fusion protein by genetically manipulated chickens

2008 ◽  
Vol 105 (5) ◽  
pp. 454-459 ◽  
Author(s):  
Kenji Kyogoku ◽  
Kazuhiro Yoshida ◽  
Hiroyuki Watanabe ◽  
Takashi Yamashita ◽  
Yoshinori Kawabe ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Fusion Protein ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Fc Fusion Protein ◽  
Genetically Manipulated ◽  
Recombinant Tumor Necrosis Factor ◽  
Necrosis Factor

scholarly journals Associations of tumor necrosis factor-α polymorphisms with the risk of colorectal cancer: a meta-analysis

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xue Huang ◽  
Shanyu Qin ◽  
Yongru Liu ◽  
Lin Tao ◽  
Haixing Jiang
Keyword(s):  
Colorectal Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Biological Marker ◽  
Recessive Model ◽  
Pilot Studies ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background: Recently, the roles of tumor necrosis factor-α (TNF-α) polymorphisms in colorectal cancer (CRC) were analyzed by some pilot studies, with inconsistent results. Therefore, we performed the present study to better assess the relationship between TNF-α polymorphisms and the risk of CRC. Methods: Eligible studies were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess correlations between TNF-α polymorphisms and CRC. Results: A total of 22 studies were included for analyses. A significant association with the risk of CRC was detected for TNF-α -308 G/A (recessive model: P = 0.004, OR = 1.42, 95%CI 1.12–1.79) polymorphism in overall analyses. Further subgroup analyses based on ethnicity of participants revealed that TNF-α -238 G/A was significantly correlated with the risk of CRC in Caucasians (dominant model: P = 0.01, OR = 0.47, 95%CI 0.26–0.86; overdominant model: P = 0.01, OR = 2.27, 95%CI 1.20–4.30; allele model: P = 0.02, OR = 0.51, 95%CI 0.29–0.90), while -308 G/A polymorphism was significantly correlated with the risk of CRC in Asians (recessive model: P = 0.001, OR = 2.23, 95%CI 1.38–3.63). Conclusions: Our findings indicated that TNF-α -238 G/A polymorphism may serve as a potential biological marker for CRC in Caucasians, and TNF-α -308 G/A polymorphism may serve as a potential biological marker for CRC in Asians.

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