scholarly journals Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223773 ◽  
Author(s):  
Lara Maria Kalempa Demeu ◽  
Rodrigo Jahn Soares ◽  
Juliana Severo Miranda ◽  
Lisandro A. Pacheco-Lugo ◽  
Kelin Gonçalves Oliveira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Invasion ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Metacyclic Trypomastigotes

scholarly journals Infection by Trypanosoma cruzi Metacyclic Forms Deficient in gp82 but Expressing a Related Surface Molecule, gp30

2003 ◽  
Vol 71 (11) ◽  
pp. 6184-6191 ◽  
Author(s):  
Mauro Cortez ◽  
Ivan Neira ◽  
Daniele Ferreira ◽  
Alejandro O. Luquetti ◽  
Anis Rassi ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cell Invasion ◽  
Target Cell ◽  
Surface Profile ◽  
Cell Entry ◽  
Gastric Mucin ◽  
Surface Glycoprotein ◽  
Metacyclic Trypomastigotes ◽  
Mucosal Infection

ABSTRACT Trypanosoma cruzi metacyclic trypomastigotes invade and replicate in the gastric mucosal epithelium after oral infection. In this study we analyzed the process of infection by T. cruzi isolates deficient in the expression of gp82, the metacyclic stage-specific surface glycoprotein implicated in target cell entry in vitro and in promoting mucosal infection in mice after oral challenge. Mice infected by the oral route with metacyclic forms of gp82-deficient isolate 569 or 588 developed patent parasitemia but at greatly reduced levels compared to those infected with the gp82-expressing isolate CL. Metacyclic forms of both isolates expressed gp30, a surface glycoprotein detectable by monoclonal antibody (MAb) 3F6 directed to gp82. Otherwise, the gp82-deficient isolates displayed a surface profile similar to that of the CL isolate and also entered epithelial HeLa cells in a manner inhibitable by MAb 3F6 and dependent on the parasite signal transduction that involved the activation of protein tyrosine kinase and Ca2+ mobilization from thapsigargin-sensitive stores. Like gp82, gp30 triggered the host cell Ca2+ response required for parasite internalization. Purified gp30 and the recombinant gp82 inhibited HeLa cell invasion of metacyclic forms of isolates 569 and 588 by ∼90 and ∼70%, respectively. A cell invasion assay performed in the presence of gastric mucin, mimicking the in vivo infection, showed an inhibition of 70 to 75% in the internalization of gp82-deficient isolates but not of the CL isolate. The recombinant gp82 exhibited an adhesive capacity toward gastric mucin much higher than that of gp30. Taken together, our findings indicate that target cell entry of metacyclic trypomastigotes can be mediated either by gp82 or gp30 but that efficient mucosal infection depends on the expression of gp82.

scholarly journals A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

2010 ◽  
Vol 59 (11) ◽  
pp. 1665-1674 ◽  
Author(s):  
Merete Thune Wiiger ◽  
Hege B. Gehrken ◽  
Øystein Fodstad ◽  
Gunhild M. Mælandsmo ◽  
Yvonne Andersson
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Tumour Growth ◽  
Cancer Cell Invasion ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Antibody Targeting

Single-chain Antibody Against Reg4 Suppresses Gastric Cancer Cell Growth and Enhances 5-FU-induced Cell Death in vitro

2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Ags Cells ◽  
Thiazolyl Blue Tetrazolium Bromide

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

Single-chain antibody-decorated Au nanocages@liposomal layer nanoprobes for targeted SERS imaging and remote-controlled photothermal therapy of melanoma cancer cells

2021 ◽  
Vol 124 ◽  
pp. 112086
Author(s):  
Ghazal Farahavar ◽  
Samira Sadat Abolmaali ◽  
Foroogh Nejatollahi ◽  
Amin Safaie ◽  
Sanaz Javanmardi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Photothermal Therapy ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Melanoma Cancer ◽  
Sers Imaging
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