Abstract P035: A promising cancer immunotherapy target: Novel fully human agonist antibodies against the human T-cell costimulatory receptor CD27

2022 ◽  
Author(s):  
Yulia Ovechkina ◽  
Shaarwari Sridhar ◽  
David Jurchen ◽  
David Peckham ◽  
Eric Tarcha ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Costimulatory Receptor ◽  
Human T Cell ◽  
Immunotherapy Target

scholarly journals T cell co-stimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

2016 ◽  
Author(s):  
Enfu Hui ◽  
Jeanne Cheung ◽  
Jing Zhu ◽  
Xiaolei Su ◽  
Marcus J. Taylor ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Cell Receptor ◽  
Costimulatory Receptor ◽  
T Cell Function ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immunotherapy Target

AbstractProgrammed death-1 (PD-1) is a co-inhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). Here, by titrating the strength of PD-1 signaling in both biochemical reconstitution systems and in T cells, we demonstrate that the coreceptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1- recruited Shp2 phosphatase. We also show that PD-1 colocalizes with the costimulatory receptor CD28 in plasma membrane microclusters but partially segregates from the TCR. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways may play unexpected roles in regulating effector T cell function and therapeutic responses to anti-PD-L1/PD-1.

Abstract 1246: Development of an agonistic antibody against the human T-cell costimulatory receptor CD27 as a potential immunotherapeutic tool.

2013 ◽  
Author(s):  
Hans van Eenennaam ◽  
Elise Veraar ◽  
Winfried Mulder ◽  
Ellen Bastiaanssen ◽  
Lilian Driessen ◽  
...  
Keyword(s):  
T Cell ◽  
Agonistic Antibody ◽  
Costimulatory Receptor ◽  
Human T Cell

scholarly journals High throughput functional screening for next generation cancer immunotherapy using droplet-based microfluidics

2020 ◽  
Author(s):  
Yuan Wang ◽  
Ruina Jin ◽  
Bingqing Shen ◽  
Na Li ◽  
He Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
High Throughput ◽  
Low Frequency ◽  
Full Potential ◽  
Functional Screening ◽  
Next Generation ◽  
Costimulatory Receptor ◽  
Lentivirus Transduction ◽  
Bispecific T Cell Engager

AbstractCurrently high throughput approaches are lagged for isolation of antibodies whose function goes beyond simple binding, which have prevented the next generation cancer immunotherapeutics, such as bispecific T cell engager antibodies or agonist antibody of costimulatory receptor, from reaching their full potential. Here we developed a highly efficient droplet-based microfluidics platform combining with lentivirus transduction system that enables functional screening of millions of antibodies. To showcase the capacity of the system, functional antibodies for CD40 agonism with low frequency (<0.02%) were identified with 2 rounds of screening. To demonstrate its versatility, an anti-Her2/anti-CD3 bispecific antibody library was established using bispecific T cell Engager (BiTE) platform and functional screening enabled efficient identification of potent anti-Her2/anti-CD3 BiTE antibodies. The platform could revolutionize the next generation cancer immunotherapy drug development and research world.

scholarly journals Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenqing Li ◽  
Xinfu Zhang ◽  
Chengxiang Zhang ◽  
Jingyue Yan ◽  
Xucheng Hou ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Costimulatory Molecule ◽  
Tumor Model ◽  
Antitumor Effects ◽  
Costimulatory Receptor ◽  
Receptor Mrna ◽  
Phospholipid Nanoparticles ◽  
Biomimetic Nanoparticles

AbstractAntibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.

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