Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro
Immunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematologi...
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2025.2462106 |
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| author | Danielle Craig-Meyer Joseph A. Hollenbaugh Sara Morgado Karen McGee Ethan Perkins Brogan Yarzabek Philip Lapinski Amber Rowse Chris Cooper Mara Fortunato Mario Cocco Karen Cadwallader James Munday |
| author_facet | Danielle Craig-Meyer Joseph A. Hollenbaugh Sara Morgado Karen McGee Ethan Perkins Brogan Yarzabek Philip Lapinski Amber Rowse Chris Cooper Mara Fortunato Mario Cocco Karen Cadwallader James Munday |
| author_sort | Danielle Craig-Meyer |
| collection | DOAJ |
| description | Immunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematological malignancies. However, immune checkpoint inhibitors (ICI) are not devoid of side effects, collectively regarded as immune-related adverse events (irAE); they are not easily uncovered in preclinical immunotoxicological investigations and are often due to the very low expression of their targets in immunologically-unchallenged non-clinical species. We have characterized expression of a broad range of immune checkpoint receptors in peripheral blood mononuclear cell (PBMC) subpopulations from cynomolgus monkeys and healthy human volunteers, under resting and T-cell stimulatory conditions by multicolor flow cytometry to inform appropriate species selection for modeling potential irAE in immunotherapeutic preclinical research. Focusing on the response of the main lymphocyte populations to interleukin (IL)-2 alone, or in combination with anti-CD3 and anti-CD28 antibodies, checkpoints with shared similarities and key differences between the two species were identified. The results of this first study provide a database for the expression and response to stimulation for immune checkpoint receptors and can help guide future model selection in the design of preclinical studies involving immunotherapeutics directed against these targets. |
| format | Article |
| id | doaj-art-0276c8dcde5e4d44a0a2248088d4e30e |
| institution | OA Journals |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-0276c8dcde5e4d44a0a2248088d4e30e2025-08-20T01:56:45ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012025-12-0122110.1080/1547691X.2025.2462106Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitroDanielle Craig-Meyer0Joseph A. Hollenbaugh1Sara Morgado2Karen McGee3Ethan Perkins4Brogan Yarzabek5Philip Lapinski6Amber Rowse7Chris Cooper8Mara Fortunato9Mario Cocco10Karen Cadwallader11James Munday12Labcorp Early Development Laboratories Limited, Harrogate, UKLabcorp Early Development Laboratories Inc, Greenfield, INLabcorp Early Development Laboratories Limited, Huntingdon, UKLabcorp Early Development Laboratories Limited, Harrogate, UKLabcorp Early Development Laboratories Limited, Harrogate, UKLabcorp Early Development Laboratories Inc, Ann Arbor, MILabcorp Early Development Laboratories Inc, Ann Arbor, MILabcorp Early Development Laboratories Inc, Ann Arbor, MILabcorp Early Development Laboratories Limited, Harrogate, UKLabcorp Early Development Laboratories Limited, Huntingdon, UKLabcorp Early Development Laboratories Limited, Harrogate, UKLabcorp Early Development Laboratories Limited, Huntingdon, UKLabcorp Early Development Laboratories Limited, Harrogate, UKImmunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematological malignancies. However, immune checkpoint inhibitors (ICI) are not devoid of side effects, collectively regarded as immune-related adverse events (irAE); they are not easily uncovered in preclinical immunotoxicological investigations and are often due to the very low expression of their targets in immunologically-unchallenged non-clinical species. We have characterized expression of a broad range of immune checkpoint receptors in peripheral blood mononuclear cell (PBMC) subpopulations from cynomolgus monkeys and healthy human volunteers, under resting and T-cell stimulatory conditions by multicolor flow cytometry to inform appropriate species selection for modeling potential irAE in immunotherapeutic preclinical research. Focusing on the response of the main lymphocyte populations to interleukin (IL)-2 alone, or in combination with anti-CD3 and anti-CD28 antibodies, checkpoints with shared similarities and key differences between the two species were identified. The results of this first study provide a database for the expression and response to stimulation for immune checkpoint receptors and can help guide future model selection in the design of preclinical studies involving immunotherapeutics directed against these targets.https://www.tandfonline.com/doi/10.1080/1547691X.2025.2462106Immune checkpoint receptorsimmune checkpoint inhibitorsimmunotherapyimmunotoxicologypreclinical drug developmentcynomolgus monkey |
| spellingShingle | Danielle Craig-Meyer Joseph A. Hollenbaugh Sara Morgado Karen McGee Ethan Perkins Brogan Yarzabek Philip Lapinski Amber Rowse Chris Cooper Mara Fortunato Mario Cocco Karen Cadwallader James Munday Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro Journal of Immunotoxicology Immune checkpoint receptors immune checkpoint inhibitors immunotherapy immunotoxicology preclinical drug development cynomolgus monkey |
| title | Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro |
| title_full | Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro |
| title_fullStr | Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro |
| title_full_unstemmed | Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro |
| title_short | Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions in vitro |
| title_sort | immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in t cell stimulatory conditions in vitro |
| topic | Immune checkpoint receptors immune checkpoint inhibitors immunotherapy immunotoxicology preclinical drug development cynomolgus monkey |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2025.2462106 |
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