human tumor xenografts
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2021 ◽  
Vol 22 (4) ◽  
pp. 1069-1074
Author(s):  
Jutatip Panaampon ◽  
Kenichi Sasamoto ◽  
Ryusho Kariya ◽  
Seiji Okada

2021 ◽  
Vol 9 (1) ◽  
pp. e002025
Author(s):  
Marcus P Kelly ◽  
Sosina Makonnen ◽  
Carlos Hickey ◽  
T Cody Arnold ◽  
Jason T Giurleo ◽  
...  

BackgroundProgrammed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blocking antibodies including cemiplimab have generated profound clinical activity across diverse cancer types. Tumorous PD-L1 expression, as assessed by immunohistochemistry (IHC), is an accepted predictive marker of response to therapy in some cancers. However, expression is often dynamic and heterogeneous, and therefore not reliably captured by IHC from tumor biopsies or archival samples. Thus, there is significant need for accurate whole-body quantification of PD-L1 levels.MethodsWe radiolabeled the novel human anti-PD-L1 antibody REGN3504 with zirconium-89 (89Zr) using the chelator p-SCN-Bn-Deferoxamine to enable non-invasive immuno-positron emission tomography (immuno-PET) of PD-L1 expression. PET imaging assessed the localization of 89Zr-REGN3504 to multiple human tumor xenografts. Mice genetically humanized for PD-1 and PD-L1 were used to assess the biodistribution of 89Zr-REGN3504 to normal tissues and the estimated human radiation dosimetry of 89Zr-REGN3504 was also determined. Pharmacokinetics of REGN3504 was assessed in monkeys.ResultsClear localization of 89Zr-REGN3504 to human tumor xenografts was observed via PET imaging and ex vivo biodistribution studies demonstrated high (fourfold to sixfold) tumor:blood ratios. 89Zr-REGN3504 specifically localized to spleen and lymph nodes in the PD-1/PD-L1 humanized mice. 89Zr-REGN3504 immuno-PET accurately detected a significant reduction in splenic PD-L1 positive cells following systemic treatment with clodronate liposomes. Radiation dosimetry suggested absorbed doses would be within guidelines for other 89Zr radiolabeled, clinically used antibodies. Pharmacokinetics of REGN3504 was linear.ConclusionThis work supports the clinical translation of 89Zr-REGN3504 immuno-PET for the assessment of PD-L1 expression. Future clinical studies will aim to investigate the utility of 89Zr-REGN3504 immuno-PET for predicting and monitoring response to anti-PD-1 therapy.


Author(s):  
Fallon K. Noto ◽  
Kamesh Ravi ◽  
Angela Arey ◽  
Christopher McClain ◽  
Wei Zhang ◽  
...  

2018 ◽  
Author(s):  
Kamesh Ravi ◽  
Fallon Noto ◽  
Christopher McClain ◽  
Angela Arey ◽  
Goutham Narla ◽  
...  

Tumor Biology ◽  
2017 ◽  
Vol 39 (10) ◽  
pp. 101042831773481 ◽  
Author(s):  
Janneta Tcherkassova ◽  
Sergei Tsurkan ◽  
Galina Smirnova ◽  
Julia Borisova ◽  
Ricardo Moro ◽  
...  

Author(s):  
David J. Agorku ◽  
Stefan Tomiuk ◽  
Kerstin Klingner ◽  
Stefan Wild ◽  
Silvia Rüberg ◽  
...  

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