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Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

ABSTRACT: - 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.- 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.- 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).- 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.- 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.

SUBMITTER: Chandramohan V

PROVIDER: S-EPMC6051547 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

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Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

Chandramohan Vidyalakshmi V Bryant Jeffrey D JD Piao Hailan H Keir Stephen T ST Lipp Eric S ES Lefaivre Michaela M Perkinson Kathryn K Bigner Darell D DD Gromeier Matthias M McLendon Roger E RE

Archives of pathology & laboratory medicine 20170822 12

<h4>Context</h4>- 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 ...[more]

PMID: 28829151

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Project description:BackgroundBladder cancer is an aggressive and heterogeneous disease associated with high morbidity and mortality. And poliovirus receptor (PVR or CD155) played crucial roles in tumor immune microenvironment and cancer development. However, their association remains obscure.MethodsA total of 797 patients from TCGA and GEO databases were employed in our study, in which 285 cases were set as the training cohort and 512 were defined as the validation cohort. Our own Xiangya cohort with 57 samples was also used for the validation. Survival differences were evaluated by Kaplan-Meier analysis between groups. The immune infiltration was evaluated by ESTIMATE, TIMER, and CIBERSORT algorithms. The risk signature was constructed by LASSO Cox regression analysis. And a nomogram model was generated subsequent to the multivariate Cox proportional hazards analysis to predict 3- and 5-year survival of patients with bladder cancer.ResultsPVR was overexpressed across various cancers including bladder cancer and related to poorer overall survival in bladder urothelial carcinoma (BLCA). Samples with higher World Health Organization (WHO) grade or higher tumor stage tended to express higher level of PVR. And PVR-related genes were involved in several immune processes and oncological pathways. When the patients were divided into low- and high-risk groups based on their risk scores, we found that patients in the high-risk group had shorter overall survival time. Besides, samples with high risk were consistently correlated with tumor hallmarks and higher abundance of immune infiltration. Additionally, chemotherapy showed potent efficacy in high-risk group. Moreover, a nomogram including clinicopathologic features and the established risk signature could predict 3- and 5-year survival in patients with bladder cancer.ConclusionOur study revealed that PVR was overexpressed and related to poor prognosis in bladder cancer. A risk signature and nomogram model based on PVR-related genes could predict the prognosis and therapeutic efficacy and were also associated with the immune infiltration in bladder cancer.

Dataset Information

Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

Publications

Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas.

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