Stabilization of Proteins by Polymer Conjugation via ATRP

2008 ◽  
Author(s):  
Jason Berberich ◽  
Lance Mabus ◽  
Virginia Depp ◽  
Bhalchandra Lele
Keyword(s):  
Polymer Conjugation

Evolution of polymer conjugation to proteins

2020 ◽  
pp. 3-22 ◽  
Author(s):  
Samuel Zalipsky ◽  
Gianfranco Pasut
Keyword(s):  
Polymer Conjugation

scholarly journals UV-Induced Tetrazole-Thiol Reaction for Polymer Conjugation and Surface Functionalization

2015 ◽  
Vol 54 (30) ◽  
pp. 8732-8735 ◽  
Author(s):  
Wenqian Feng ◽  
Linxian Li ◽  
Chengwu Yang ◽  
Alexander Welle ◽  
Oliver Trapp ◽  
...  
Keyword(s):  
Surface Functionalization ◽  
Polymer Conjugation ◽  
Thiol Reaction

An engineered immunotherapy (NKTR-214) with altered selectivity toward the IL2 receptor: Efficacy and tolerability in a murine tumor model.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3060-3060
Author(s):  
Deborah H. Charych ◽  
Murali Addepalli ◽  
Steve Lee ◽  
Thomas Chang ◽  
Xiaofeng Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Immune Cells ◽  
Tumor Model ◽  
Optimal Dose ◽  
Growth Delay ◽  
Blue Dye ◽  
Tumor Localization ◽  
Tumor Growth Delay ◽  
Polymer Conjugation

3060 Background: Cytokine-based immunotherapy has been successful for the treatment of cancer, with potential for durable responses in multiple indications. One approach towards stimulating the immune system is to target the heterotrimeric interleukin2 receptor, IL2R. NKTR-214 uses polymer technology to alter receptor subunit selectivity to favor expansion of CD8+ memory effector T cells (CD8T) in the tumor over CD4+ regulatory T cells (Treg). In addition, polymer conjugation is designed to improve exposure and enhance tumor localization, significantly improving efficacy, modulating vascular leak syndrome (VLS) and allowing flexible dosing regimens. Methods: C57BL/6 mice bearing established subcutaneous B16F10 melanoma were treated with NKTR-214 at a variety of doses (0.25-4.0 mg/kg) and schedules (q5dx3 to q14dx2). Mice treated with clinically validated IL2 were administered 3mg/kg, bidx5 for 2 cycles. Efficacy was measured by monitoring tumor volumes. Tolerability was evaluated by survival. VLS was measured by injection of Evans Blue dye followed by colorimetry in lungs. Tumor immunotyping, by flow cytometry. Results: Tumors from mice receiving NKTR-214 had a CD8/Treg ratio of over 1,000 versus 14 for IL2. NKTR-214 administered at 2 mg/kg, q9dx3 was identified as the optimal regimen and showed tumor growth delay of 26 days compared to 9 days for optimally dosed IL2. 90% of NKTR-214 treated mice tolerated treatment compared to 67% for IL2. VLS was completely resolved prior to administration of the next dose of NKTR-214, unlike IL2. NKTR-214 was well tolerated in rats at two schedules, at MTD. Conclusions: NKTR-214 is a highly differentiated cytokine with a new mechanism of action that may provide options for cancer immunotherapy. Polymer conjugation of a clinically validated cytokine alters the IL2R selectivity to favor expansion of tumor killing immune cells (CD8T) over regulatory immune cells (Treg) in the tumor. The conjugate is also designed to improve exposure and enhance tumor localization, offering more options of dose and schedule. The optimal dose and schedule is cytokine-sparing, provides substantial tumor growth delay, and reduces toxicity.

scholarly journals Site-selective enzymatic chemistry for polymer conjugation to protein lysine residues: PEGylation of G-CSF at lysine-41

2016 ◽  
Vol 7 (42) ◽  
pp. 6545-6553 ◽  
Author(s):  
A. Mero ◽  
A. Grigoletto ◽  
K. Maso ◽  
H. Yoshioka ◽  
A. Rosato ◽  
...  
Keyword(s):  
Specific Protein ◽  
Microbial Transglutaminase ◽  
Site Specific ◽  
Lysine Residues ◽  
Polymer Conjugation ◽  
Site Selective

Microbial transglutaminase (mTGase) is an enzyme that catalyzes site-specific protein derivatization at specific glutamines and lysines.

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