Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas
| Autor: | Stephen T. Keir, Matthias Gromeier, Roger E. McLendon, Michaela Lefaivre, Eric S. Lipp, Darell D. Bigner, Jeffrey D. Bryant, Kathryn Perkinson, Hailan Piao, Vidyalakshmi Chandramohan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty medicine.medical_treatment Article Pathology and Forensic Medicine 03 medical and health sciences Young Adult 0302 clinical medicine Glioma medicine Animals Humans CD155 Aged Aged 80 and over Oncolytic Virotherapy biology Brain Neoplasms Antibodies Monoclonal General Medicine Immunotherapy Middle Aged medicine.disease Immunohistochemistry Oncolytic virus Clinical trial Medical Laboratory Technology 030104 developmental biology 030220 oncology & carcinogenesis Monoclonal biology.protein Cancer research Receptors Virus Female Rabbits Glioblastoma Poliovirus Receptor |
| Zdroj: | Archives of pathologylaboratory medicine. 141(12) |
| ISSN: | 1543-2165 |
| Popis: | Context.— The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Center for Biologics Evaluation and Research. A reliable clinical assay to document expression of the poliovirus receptor, CD155, in routinely available patient tumor samples is needed for continued clinical development of PVSRIPO oncolytic immunotherapy in primary brain tumors and beyond. Objectives.— To validate a novel anti-CD155 antibody for immunohistochemistry and develop a robust, reliable, and specific protocol for detecting CD155 expression in glioblastoma formalin-fixed, paraffin-embedded (FFPE) tissue samples. To characterize the expression of CD155 in human glioblastoma cells as well as to evaluate the influence of CD155 expression levels on tumor cell susceptibility to PVSRIPO infection and killing. Design.— Immunohistochemical staining on glioblastoma FFPE tissue sections and immunoblot of corresponding frozen tissues were performed. Positive controls were confirmed sites of poliovirus propagation, spinal cord anterior horn, and tonsils; negative controls were vascular smooth muscle in patient samples and FFPE sections from a confirmed CD155-negative Burkitt lymphoma line (Raji). Results.— We succeeded in developing a reliable assay to specifically detect CD155 by immunohistochemistry in glioblastoma FFPE sections. Our data suggest widespread, virtually universal expression of CD155 in glioblastoma cells at levels commensurate with susceptibility to PVSRIPO infection and killing. Conclusions.— Anti-CD155 antibody D3G7H achieves monospecific detection of CD155 in immunoblots of tumor homogenates and immunohistochemistry of tumor FFPE sections. Our assay has utility in defining appropriate use of PVSRIPO in oncolytic immunotherapy against malignant glioma and other cancer histotypes. |
| Databáze: | OpenAIRE |
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