Identification and Validation of a PD-L1 Binding Peptide for Determination of PDL1 Expression in Tumors

PD-L1 结合肽的鉴定和验证,用于确定肿瘤中的 PDL1 表达

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作者:Charles Caldwell Jr, Cory E Johnson, V N Balaji, Govardhan A Balaji, Richard D Hammer, Raghuraman Kannan

Abstract

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.

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