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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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) |
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Immunotherapy Immune checkpoint Lymphocyte activation gene-3 Single-domain antibody Nanobody Molecular imaging Medical physics. Medical radiology. Nuclear medicine R895-920 |
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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 |
work_keys_str_mv |
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