Targeted Delivery of Anti-CTLA-4 Antibody Downregulates T Cell Function in Vitro and in Vivo

2001 ◽  
Vol 101 (2) ◽  
pp. 136-145 ◽  
Author(s):  
Seema Rao ◽  
Chenthamarakshan Vasu ◽  
Osvaldo Martinez ◽  
Shashi Kaithamana ◽  
Bellur S. Prabhakar ◽  
...  
Keyword(s):  
T Cell ◽  
Targeted Delivery ◽  
Cell Function ◽  
T Cell Function

TSR-033, a Novel Therapeutic Antibody Targeting LAG-3, Enhances T-Cell Function and the Activity of PD-1 Blockade In Vitro and In Vivo

2018 ◽  
Vol 18 (3) ◽  
pp. 632-641 ◽  
Author(s):  
Srimoyee Ghosh ◽  
Geeta Sharma ◽  
Jon Travers ◽  
Sujatha Kumar ◽  
Justin Choi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Therapeutic Antibody ◽  
T Cell Function ◽  
Antibody Targeting ◽  
Novel Therapeutic

scholarly journals Cholesterol Lowering Modulates T Cell Function In Vivo and In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e92095 ◽  
Author(s):  
Kuang-Yuh Chyu ◽  
Wai Man Lio ◽  
Paul C. Dimayuga ◽  
Jianchang Zhou ◽  
Xiaoning Zhao ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Cholesterol Lowering ◽  
T Cell Function

scholarly journals The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1134
Author(s):  
Won-Ju Kim ◽  
Gil-Ran Kim ◽  
Hyun-Jung Cho ◽  
Je-Min Choi
Keyword(s):  
Drug Delivery ◽  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Fluorescent Protein ◽  
Autoimmune Encephalomyelitis ◽  
Optimal Sequence ◽  
T Cell Function

T cells are key immune cells involved in the pathogenesis of several diseases, rendering them important therapeutic targets. Although drug delivery to T cells is the subject of continuous research, it remains challenging to deliver drugs to primary T cells. Here, we used a peptide-based drug delivery system, AP, which was previously developed as a transdermal delivery peptide, to modulate T cell function. We first identified that AP-conjugated enhanced green fluorescent protein (EGFP) was efficiently delivered to non-phagocytic human T cells. We also confirmed that a nine-amino acid sequence with one cysteine residue was the optimal sequence for protein delivery to T cells. Next, we identified the biodistribution of AP-dTomato protein in vivo after systemic administration, and transduced it to various tissues, such as the spleen, liver, intestines, and even to the brain across the blood–brain barrier. Next, to confirm AP-based T cell regulation, we synthesized the AP-conjugated cytoplasmic domain of CTLA-4, AP-ctCTLA-4 peptide. AP-ctCTLA-4 reduced IL-17A expression under Th17 differentiation conditions in vitro and ameliorated experimental autoimmune encephalomyelitis, with decreased numbers of pathogenic IL-17A+GM-CSF+ CD4 T cells. These results collectively suggest the AP peptide can be used for the successful intracellular regulation of T cell function, especially in the CNS.

CD3 limits the efficacy of TCR gene therapy in vivo

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3528-3537 ◽  
Author(s):  
Maryam Ahmadi ◽  
Judith W. King ◽  
Shao-An Xue ◽  
Cécile Voisine ◽  
Angelika Holler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Cell Receptor ◽  
Surface Expression ◽  
T Cell Function ◽  
Engineered T Cells ◽  
Rate Limiting

Abstract The function of T-cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR α/β heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T-cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T-cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognized lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared with T cells modified by TCR only. After tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when rechallenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.

scholarly journals Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Xiao-Jing Ji ◽  
Ji-Wei Hao ◽  
Guang-Lei Li ◽  
Ning Dong ◽  
Xin-Qi Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
T Cell ◽  
Sympathetic Nervous System ◽  
Cell Function ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
T Cell Function ◽  
Sympathetic Nervous

Background. Although glucagon-like peptide 1- (GLP-1-) based therapy of hyperglycemia in burn injury has shown great potential in clinical trials, its safety is seldom evaluated. We hypothesize that exendin-4, a GLP-1 analogue, might affect the immune response via the activation of the sympathetic nervous system in burn injury. Methods. Male Balb/c mice were subjected to sham or thermal injury of 15% total body surface area. Exendin-4 on T cell function in vitro was examined in cultured splenocytes in the presence of β-adrenoceptor antagonist propranolol (1 nmol/L) or GLP-1R antagonist exendin (9-39) (1 μmol/L), whereas its in vivo effect was determined by i.p. injection of exendin-4 (2.4 nmol/kg) in mice. To further elucidate the sympathetic mechanism, propranolol (30 mg/kg) or vehicle was applied 30 min prior to injury. Results. Although the exacerbated burn-induced mortality by exendin-4 was worsened by propranolol pretreatment, the inhibition of T cell proliferation by exendin-4 in vitro could be restored by propranolol instead of exendin (9-39). However, a Th2 switch by exendin-4 in vitro could only be reversed by exendin (9-39). Likewise, the inhibition of splenic T cell function and NFAT activity by exendin-4 in vivo was restored by propranolol. By contrast, the increased splenic NF-κB translocation by exendin-4 in vivo was potentiated by propranolol in sham mice but suppressed in burn mice. Accordingly, propranolol abrogated the heightened inflammatory response in the lung and the accelerated organ injuries by exendin-4 in burn mice. On the contrary, a Th2 switch and higher serum levels of inflammatory mediators by exendin-4 were potentiated by propranolol in burn mice. Lastly, exendin-4 raised serum stress hormones which could be remarkably augmented by propranolol. Conclusions. Exendin-4 suppresses T cell function and promotes organ inflammation through the activation of the sympathetic nervous system, while elicits Th2 switch via GLP-1R in burn injury.

scholarly journals Discovery and characterization of llama VHH targeting the RO form of human CD45

2020 ◽  
Author(s):  
Deepti Rokkam ◽  
Patrick J. Lupardus
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Tyrosine Phosphatase ◽  
Surface Protein ◽  
Cell Receptor ◽  
Phage Display Library ◽  
Signaling Complex ◽  
T Cell Function

AbstractCD45 is an abundant and highly active cell-surface protein tyrosine phosphatase (PTP) found on cells of hematopoietic origin. CD45 is of particular importance for T-cell function, playing a key role in the activation/inactivation cycle of the T-cell receptor signaling complex. The extracellular domain of CD45 is comprised of an N-terminal mucin-like domain which can be alternatively spliced to a core domain (RO) consisting of four domains with fibronectin 3 domain (FN3)-like topology. The study of CD45 has been hampered by a small set of publicly available antibodies, which we characterized as specific to the N-terminal FN3 domains of CD45 RO. To broaden the human CD45 reagent set, we identified anti-CD45 single domain VHH antibodies from a post-immune llama phage display library. Using a yeast display domain mapping system and affinity measurement we characterized seven unique clonotypes specific for CD45 RO, including binders that target each of the four FN3-like domains. These VHH molecules are important new tools for studying the role of CD45 in T-cell function in vitro and in vivo.

Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo

2006 ◽  
Vol 15 (8) ◽  
pp. 634-642 ◽  
Author(s):  
Simone Rubant ◽  
Ralf J. Ludwig ◽  
Jeannette Pfeffer ◽  
Petra Schulze-Johann ◽  
Roland Kaufmann ◽  
...  
Keyword(s):  
T Cell ◽  
Receptor Antagonist ◽  
Chemokine Receptor ◽  
Broad Spectrum ◽  
Cell Function ◽  
Eukaryotic Expression ◽  
Chemokine Receptor Antagonist ◽  
T Cell Function

Immunodeficiency and other clinical immunology *1Nedocromil sodium inhibits T-cell function in vitro and in vivo

1993 ◽  
Vol 91 (3) ◽  
pp. 817-824 ◽  
Author(s):  
Y MEKORI ◽  
D BARAM ◽  
A GOLDBERG ◽  
R HERSHKOVIZ ◽  
T RESHEF ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Immunology ◽  
Cell Function ◽  
T Cell Function

scholarly journals Photoswitchable CAR-T Cell Function In Vitro and In Vivo via a Cleavable Mediator

2020 ◽  
Author(s):  
Bo Zhang ◽  
Yan Wang ◽  
Shenlong Huang ◽  
Jiaqi Sun ◽  
Min Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Car T Cell ◽  
T Cell Function ◽  
Car T
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