Identification and Validation of a PD-L1 Binding Peptide for Determination of PDL1 Expression in Tumors
| Autor: | Raghuraman Kannan, Cory E. Johnson, Richard D. Hammer, Charles W. Caldwell, Govardhan A. Balaji, Vitukudi Narayanaiyengar Balaji |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein Conformation lcsh:Medicine Peptides Cyclic Sensitivity and Specificity B7-H1 Antigen Article Flow cytometry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Neoplasms PD-L1 Biomarkers Tumor medicine Humans lcsh:Science Multidisciplinary medicine.diagnostic_test biology business.industry Melanoma lcsh:R medicine.disease Immunohistochemistry Lymphoma 030104 developmental biology Antigen retrieval chemistry 030220 oncology & carcinogenesis biology.protein Cancer research lcsh:Q Antibody business Clone (B-cell biology) Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Blocking the interaction between Programmed Death Ligand 1 (PD-L1) and its receptor, PD-1, is an effective method of treating many types of cancers. Certain tumors overexpress PD-L1, causing host immune cells that express PD-1 to bind PD-L1 and cease killing the tumor. Inhibition of PD-L1 and PD-1 binding can restore host immunity towards tumor killing, and many new drugs have been developed to target this interaction. Current methods of PD-L1 diagnosis have shown to vary based on the antibody, detection kit brand, antigen retrieval method, and clinically defined methods by the FDA. To refine detection of PD-L1, we have identified a peptide, RK-10, and used it to detect PD-L1 expressing tumors with immunohistochemistry or flow cytometry. Flow cytometry was performed on cell lines and patient tissues using a fluorescent peptide (RK-10-Cy5). Immunohistochemistry using a biotin-modified peptide (RK-10-Biotin) was tested against the FDA-approved SP263 clone on biopsied patient tissues. For this study, we evaluated specificity of RK-10 using IHC in over 200 patient tissues, including NSCLC and Hodgkin’s Lymphoma. RK-10 shows staining in the tumor regions of FFPE tissues where the SP263 kit does not. RK-10-Cy5 peptide also demonstrates PD-L1 detection in NSCLC, breast, squamous cell carcinoma, and melanoma. |
| Databáze: | OpenAIRE |
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