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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2021-11-01
|
| Series: | EJNMMI Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13550-021-00857-9 |
| _version_ | 1818724239347286016 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T21:23:15Z |
| format | Article |
| id | doaj.art-0430de807ba24283850dbe2c50c599d5 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-17T21:23:15Z |
| publishDate | 2021-11-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-0430de807ba24283850dbe2c50c599d52022-12-21T21:32:05ZengSpringerOpenEJNMMI Research2191-219X2021-11-0111111310.1186/s13550-021-00857-9Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancerQ. Lecocq0P. Debie1J. Puttemans2R. M. Awad3L. De Beck4T. Ertveldt5Y. De Vlaeminck6C. Goyvaerts7G. Raes8M. Keyaerts9K. Breckpot10N. Devoogdt11Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselIn Vivo Cellular and Molecular Imaging Laboratory, Department of Medical Imaging, Vrije Universiteit BrusselIn Vivo Cellular and Molecular Imaging Laboratory, Department of Medical Imaging, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselMyeloid Cell Immunology Laboratory, VIB Center for Inflammation ResearchIn Vivo Cellular and Molecular Imaging Laboratory, Department of Medical Imaging, Vrije Universiteit BrusselLaboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences, Vrije Universiteit BrusselIn Vivo Cellular and Molecular Imaging Laboratory, Department of Medical Imaging, Vrije Universiteit BrusselAbstract 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.https://doi.org/10.1186/s13550-021-00857-9ImmunotherapyImmune checkpointLymphocyte activation gene-3Single-domain antibodyNanobodyMolecular imaging |
| spellingShingle | 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 EJNMMI Research Immunotherapy Immune checkpoint Lymphocyte activation gene-3 Single-domain antibody Nanobody Molecular imaging |
| title | 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_short | 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 |
| topic | Immunotherapy Immune checkpoint Lymphocyte activation gene-3 Single-domain antibody Nanobody Molecular imaging |
| url | https://doi.org/10.1186/s13550-021-00857-9 |
| work_keys_str_mv | AT qlecocq evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT pdebie evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT jputtemans evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT rmawad evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT ldebeck evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT tertveldt evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT ydevlaeminck evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT cgoyvaerts evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT graes evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT mkeyaerts evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT kbreckpot evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer AT ndevoogdt evaluationofsingledomainantibodiesasnucleartracersforimagingoftheimmunecheckpointreceptorhumanlymphocyteactivationgene3incancer |