single chain
Recently Published Documents


TOTAL DOCUMENTS

6032
(FIVE YEARS 1003)

H-INDEX

127
(FIVE YEARS 13)

2022 ◽  
Author(s):  
Hanyu Pan ◽  
Jing Wang ◽  
Huitong Liang ◽  
Zhengtao Jiang ◽  
Lin Zhao ◽  
...  

HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4+ T cells that express virus either spontaneously or after intentional latency reversal. However, the T-cell exhaustion and the patient-specific autologous paradigm of CAR-T hurdled the clinical application. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 CAR (3BE CAR) construct that enables the expression of PD-1 blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). In comparison with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater anti-HIV potency with stronger proliferation capability, higher killing efficiency (up to ~75%) and enhanced cytokine secretion in the presence of HIV envelope glycoprotein-expressing cells. Furthermore, our approach achieved high levels (over 97%) of the TCR-deficient 3BE CAR-T cells with the functional inactivation of endogenous TCR to avoid graft-versus-host disease without compromising their antiviral activity relative to standard anti-HIV CAR-T cells. These data suggest that we have provided a feasible approach to large-scale generation of "off-the-shelf" anti-HIV CAR-T cells in combination with antibody therapy of PD-1 blockade, which can be a powerful therapeutic candidate for the functional cure of HIV.


2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Kenichiro Ito ◽  
Yoshihiko Matsuda ◽  
Ayako Mine ◽  
Natsuki Shikida ◽  
Kazutoshi Takahashi ◽  
...  

AbstractMimetics of growth factors and cytokines are promising tools for culturing large numbers of cells and manufacturing regenerative medicine products. In this study, we report single-chain tandem macrocyclic peptides (STaMPtides) as mimetics in a new multivalent peptide format. STaMPtides, which contain two or more macrocyclic peptides with a disulfide-closed backbone and peptide linkers, are successfully secreted into the supernatant by Corynebacterium glutamicum-based secretion technology. Without post-secretion modification steps, such as macrocyclization or enzymatic treatment, bacterially secreted STaMPtides form disulfide bonds, as designed; are biologically active; and show agonistic activities against respective target receptors. We also demonstrate, by cell-based assays, the potential of STaMPtides, which mimic growth factors and cytokines, in cell culture. The STaMPtide technology can be applied to the design, screening, and production of growth factor and cytokine mimetics.


Author(s):  
Jing Guo ◽  
Shuai He ◽  
Yongjie Zhu ◽  
Wei Yu ◽  
Dong Yang ◽  
...  

CD30-directed chimeric antigen receptors (CARs) with single chain antibody fragment (scFv)-binding domains from murine HRS3 show strong cytotoxicity to Hodgkin’s Lymphoma cells and have been used in clinical trials. However, murine scFv in CAR might induce specific rejective immune responses in patients, which compromises the therapeutic effects. The use of human or humanized antibody fragments for CAR construction, rather than those derived from mouse antibodies, can reduce the immunogenicity of the CAR. Importantly, this strategy might simultaneously decrease the risk of cytokine-mediated toxicities and improve CAR T cell persistence. Murine HRS3 antibody has been successfully humanized by grafting the complementarity-determining regions (CDRs) from the mouse antibody framework onto human immunoglobulin consensus sequences, followed by an in vitro evolutionary strategy to select functional Fab fragments with the same affinity as murine sources. In this study, humanized scFvs were utilized to construct a CD30-directed CAR (hHRS3-CAR), and its effectiveness was compared with that of HRS3-CAR. The hHRS3-CAR-T cells specifically kill CD30-positive tumor cell lines in vitro and eliminate lymphoma xenografts in immunodeficient mice with comparable efficiency to HRS3-CAR. The hHRS-CAR-T could be used in clinical trials based on the previously reported advantages of humanized CARs, such as the reduction of immune rejection and better persistence of cells.


2022 ◽  
Author(s):  
Nikhil Malik ◽  
Manmohan Aseri ◽  
Param Vir Singh ◽  
Kannan Srinivasan

Bitcoin falls dramatically short of the scale provided by banks for payments. Currently, its ledger grows by the addition of blocks of ∼2,000 transactions every 10 minutes. Intuitively, one would expect that increasing the block capacity would solve this scaling problem. However, we show that increasing the block capacity would be futile. We analyze strategic interactions of miners, who are heterogeneous in their power over block addition, and users, who are heterogeneous in the value of their transactions, using a game-theoretic model. We show that a capacity increase can facilitate large miners to tacitly collude—artificially reversing back the capacity via strategically adding partially filled blocks in order to extract economic rents. This strategic partial filling crowds out low-value payments. Collusion is sustained if the smallest colluding miner has a share of block addition power above a lower bound. We provide empirical evidence of such strategic partial filling of blocks by large miners of Bitcoin. We show that a protocol design intervention can breach the lower bound and eliminate collusion. However, this also makes the system less secure. On the one hand, collusion crowds out low-value payments; on the other hand, if collusion is suppressed, security threatens high-value payments. As a result, it is untenable to include a range of payments with vastly different outside options, willingness to bear security risk, and delay onto a single chain. Thus, we show economic limits to the scalability of Bitcoin. Under these economic limits, collusive rent extraction acts as an effective mechanism to invest in platform security and build responsiveness to demand shocks. These traits are otherwise hard to attain in a disintermediated setting owing to the high cost of consensus. This paper was accepted by Kartik Hosanagar, information systems.


2022 ◽  
Vol 44 (1) ◽  
pp. 301-308
Author(s):  
Sun-Hee Kim ◽  
Hee-Jin Jeong

Immunocytokines, antibody-cytokine fusion proteins, have the potential to improve the therapeutic index of cytokines by delivering the cytokine to the site of localized tumor cells using antibodies. In this study, we produced a recombinant anti-programmed death-ligand 1 (PD-L1) scFv, an antibody fragment against PD-L1 combined with a Neo2/15, which is an engineered interleukin with superior function using an E. coli expression system. We expressed the fusion protein in a soluble form and purified it, resulting in high yield and purity. The high PD-L1-binding efficiency of the fusion protein was confirmed via enzyme-linked immunosorbent assay, suggesting the application of this immunocytokine as a cancer-related therapeutic agent.


Author(s):  
Pietro Renna ◽  
Cristian Ripoli ◽  
Onur Dagliyan ◽  
Francesco Pastore ◽  
Marco Rinaudo ◽  
...  

Polymers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 250
Author(s):  
Chih-Hao Chang ◽  
Chih-Hung Chang ◽  
Ya-Wen Yang ◽  
Hsuan-Yu Chen ◽  
Shu-Jyuan Yang ◽  
...  

In this study, a novel polystyrene-block-quaternized polyisoprene amphipathic block copolymer (PS-b-PIN) is derived from anionic polymerization. Quaternized polymers are prepared through post-quaternization on a functionalized polymer side chain. Moreover, the antibacterial activity of quaternized polymers without red blood cell (RBCs) hemolysis can be controlled by block composition, side chain length, and polymer morphology. The solvent environment is highly related to the polymer morphology, forming micelles or other structures. The polymersome formation would decrease the hemolysis and increase the electron density or quaternized groups density as previous research and our experiment revealed. Herein, the PS-b-PIN with N,N-dimethyldodecylamine as side chain would form a polymersome structure in the aqueous solution to display the best inhibiting bacterial growth efficiency without hemolytic effect. Therefore, the different single-chain quaternized groups play an important role in the antibacterial action, and act as a controllable factor.


Biosensors ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 30
Author(s):  
Kameshpandian Paramasivam ◽  
Yuanzhao Shen ◽  
Jiasheng Yuan ◽  
Ibtesam Waheed ◽  
Chuanbin Mao ◽  
...  

Bacteriophages, abbreviated as “phages”, have been developed as emerging nanoprobes for the detection of a wide variety of biological species, such as biomarker molecules and pathogens. Nanosized phages can display a certain length of exogenous peptides of arbitrary sequence or single-chain variable fragments (scFv) of antibodies that specifically bind to the targets of interest, such as animal cells, bacteria, viruses, and protein molecules. Metal nanoparticles generally have unique plasmon resonance effects. Metal nanoparticles such as gold, silver, and magnetism are widely used in the field of visual detection. A phage can be assembled with metal nanoparticles to form an organic–inorganic hybrid probe due to its nanometer-scale size and excellent modifiability. Due to the unique plasmon resonance effect of this composite probe, this technology can be used to visually detect objects of interest under a dark-field microscope. In summary, this review summarizes the recent advances in the development of phage-based probes for ultra-sensitive detection of various bio-species, outlining the advantages and limitations of detection technology of phage-based assays, and highlighting the commonly used editing technologies of phage genomes such as homologous recombination and clustered regularly interspaced palindromic repeats/CRISPR-associated proteins system (CRISPR-Cas). Finally, we discuss the possible scenarios for clinical application of phage-probe-based detection methods.


Sign in / Sign up

Export Citation Format

Share Document