Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer

Abstract Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patien...

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Autores principales: Q. Lecocq, P. Debie, J. Puttemans, R. M. Awad, L. De Beck, T. Ertveldt, Y. De Vlaeminck, C. Goyvaerts, G. Raes, M. Keyaerts, K. Breckpot, N. Devoogdt
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Publicado: SpringerOpen 2021
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spelling oai:doaj.org-article:0430de807ba24283850dbe2c50c599d52021-11-08T10:45:46ZEvaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer10.1186/s13550-021-00857-92191-219Xhttps://doaj.org/article/0430de807ba24283850dbe2c50c599d52021-11-01T00:00:00Zhttps://doi.org/10.1186/s13550-021-00857-9https://doaj.org/toc/2191-219XAbstract Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.Q. LecocqP. DebieJ. PuttemansR. M. AwadL. De BeckT. ErtveldtY. De VlaeminckC. GoyvaertsG. RaesM. KeyaertsK. BreckpotN. DevoogdtSpringerOpenarticleImmunotherapyImmune checkpointLymphocyte activation gene-3Single-domain antibodyNanobodyMolecular imagingMedical physics. Medical radiology. Nuclear medicineR895-920ENEJNMMI Research, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunotherapy
Immune checkpoint
Lymphocyte activation gene-3
Single-domain antibody
Nanobody
Molecular imaging
Medical physics. Medical radiology. Nuclear medicine
R895-920
spellingShingle Immunotherapy
Immune checkpoint
Lymphocyte activation gene-3
Single-domain antibody
Nanobody
Molecular imaging
Medical physics. Medical radiology. Nuclear medicine
R895-920
Q. Lecocq
P. Debie
J. Puttemans
R. M. Awad
L. De Beck
T. Ertveldt
Y. De Vlaeminck
C. Goyvaerts
G. Raes
M. Keyaerts
K. Breckpot
N. Devoogdt
Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
description Abstract Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.
format article
author Q. Lecocq
P. Debie
J. Puttemans
R. M. Awad
L. De Beck
T. Ertveldt
Y. De Vlaeminck
C. Goyvaerts
G. Raes
M. Keyaerts
K. Breckpot
N. Devoogdt
author_facet Q. Lecocq
P. Debie
J. Puttemans
R. M. Awad
L. De Beck
T. Ertveldt
Y. De Vlaeminck
C. Goyvaerts
G. Raes
M. Keyaerts
K. Breckpot
N. Devoogdt
author_sort Q. Lecocq
title Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
title_short Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
title_full Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
title_fullStr Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
title_full_unstemmed Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
title_sort evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
publisher SpringerOpen
publishDate 2021
url https://doaj.org/article/0430de807ba24283850dbe2c50c599d5
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