[EN] DC-SIGN ANTIBODY CONJUGATES COMPRISING STING AGONISTS<br/>[FR] CONJUGUÉS D'ANTICORPS DC-SIGN COMPRENANT DES AGONISTES DE STING
申请人:NOVARTIS AG
公开号:WO2020092617A1
公开(公告)日:2020-05-07
Provided herein are immunoconjugates comprising an anti-DC-SiGN antibody conjugated to a STING agonist. Also disclosed are methods of making the immunoconjugates and methods of treating cancer using the immunoconjugates.
作者:Valerie Spieler、Marie-Gabrielle Ludwig、Janet Dawson、Bruno Tigani、Amanda Littlewood-Evans、Caterina Safina、Hilmar Ebersbach、Klaus Seuwen、Martina Raschig、Björn ter Mors、Thomas D. Müller、Lorenz Meinel、Tessa Lühmann
DOI:10.1016/j.jconrel.2020.07.005
日期:2020.10
Anti-inflammatory cytokines are a promising class of therapeutics for treatment of rheumatoid arthritis (RA), but their use is currently limited by a rapid clearance and systemic toxicity. Interleukin-4 is a small cytokine with potential for RA therapy. To increase its pharmacokinetic features, we engineered a murine IL4 conjugate by incorporating an unnatural amino acid through genetic code expansion to which PEG-folate, as a targeting moiety and PEG alone as control, were site-specifically bound. Both IL4 conjugates retained bioactivity and induced primary murine macrophage polarization into an alternatively activated (M2) related phenotype. The PEGylated conjugates had a terminal half-life of about four hours in healthy mice compared to unPEGylated IL4 (0.76 h). We showed that both conjugates successfully accumulated into arthritic joints in an antigen-induced arthritis (AIA) mouse model, as assessed by non-invasive fluorescence imaging. The modular nature of the IL4 conjugate chemistry presented herein facilitates easy adaption of PEG chain length and targeting moieties for further improvement of half-life and targeting function for future efficacy studies.
MUTANT VIRUS, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
申请人:PEKING UNIVERSITY
公开号:US20200268870A1
公开(公告)日:2020-08-27
The present invention relates to a mutated virus. Said virus can be an influenza virus of human or other animal origin. The present invention also relates to a method for preparing the mutated virus, the method comprising introducing UAG codons into positions upstream of the stop codons per se of one or more genes of a viral genome by reverse genetic techniques. The present invention further relates to uses of the mutated virus, for example, as a live attenuated vaccine, or in replication of controllable and safe virus models, and the like.
Genetic Encoding and Labeling of Aliphatic Azides and Alkynes in Recombinant Proteins <i>via</i> a Pyrrolysyl-tRNA Synthetase/tRNA<sub>CUA</sub> Pair and Click Chemistry
作者:Duy P. Nguyen、Hrvoje Lusic、Heinz Neumann、Prashant B. Kapadnis、Alexander Deiters、Jason W. Chin
DOI:10.1021/ja900553w
日期:2009.7.1
recombinant proteins in Escherichia coli. Proteins containing the alkyne functional group are labeled with an azido biotin and an azido fluorophore, via copper catalyzed [3+2] cycloaddition reactions, to produce the corresponding triazoles in good yield. The methods reported are useful for the site-specific labeling of recombinant proteins and may be combined with mutually orthogonal methods of introducing