ENTPD1/CD39 as a predictive marker of treatment response to gemogenovatucel-T as maintenance therapy in newly diagnosed ovarian cancer

• Published in: Communications medicine Vol. 2; no. 1; pp. 106 - 9
• Main Authors: Rocconi, Rodney P., Stanbery, Laura, Tang, Min, Madeira da Silva, Luciana, Walter, Adam, Monk, Bradley J., Herzog, Thomas J., Coleman, Robert L., Manning, Luisa, Wallraven, Gladice, Horvath, Staci, Bognar, Ernest, Senzer, Neil, Brun, Scott, Nemunaitis, John
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.08.2022; Springer Nature B.V; Nature Portfolio
• Subjects: 38; 631/67; 692/53; Biomarkers; Cancer therapies; Demographics; Gene expression; Immunotherapy; Medicine; Medicine & Public Health; Oncology; Ovarian cancer; Patients; Tumors; Vaccines; United States > US; Biomarkers; Cancer
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-022-00163-y

Background Broadened use of predictive molecular and phenotypic profiling amongst oncologists has facilitated optimal integration of targeted- and immuno-therapeutics into clinical care. However, the use of predictive immunomarkers in ovarian cancer (OC) has not consistently translated into clinical benefit. Vigil (gemogenovatucel-T) is a novel plasmid engineered autologous tumor cell immunotherapy designed to knock down the tumor suppressor cytokines, TGFβ1 and TGFβ2, augment local immune function via increased GMCSF expression and enhance presentation of clonal neoantigen epitopes. Methods All patients enrolled in the VITAL trial (NCT02346747) of maintenance Vigil vs. placebo as front-line therapy with homologous recombination proficient (HRP) stage IIIB-IV newly diagnosed ovarian cancer underwent NanoString gene expression analysis. Tissue was obtained from surgically resected ovarian tumor tissue following surgical debulking. A statistical algorithm was used to analyze the NanoString gene expression data. Results Using the NanoString Statistical Algorithm (NSA), we identify high expression of ENTPD1/CD39 (which functions as the rate-limiting step in the production of the immune suppressor adenosine from ATP to ADP) as a presumptive predictor of response to Vigil versus placebo regardless of HRP status on the basis of relapse free survival (median not achieved vs 8.1 months, p  = 0.00007) and overall survival (median not achieved vs 41.4 months, p  = 0.013) extension. Conclusion NSA should be considered for application to investigational targeted therapies in order to identify populations most likely to benefit from treatment, in preparation for efficacy conclusive trials. Plain Language Summary Treatment options are limited in patients with advanced stage ovarian cancer. Treatments that stimulate the immune system to target the cancer are sometimes effective, however determining which patients will have benefit has been difficult. It is therefore important to develop new markers to predict which patients will respond to therapy. In this study, we looked at the levels of a large number of genes in tumors from patients treated with Vigil (gemogenovatucel-T), a treatment that modifies patient’s own tumor cells to activate the immune system. We demonstrate that high expression of a gene named ENTPD1 / CD39 predicts a positive response to Vigil therapy. This finding could help clinicians to determine which patients might benefit from Vigil treatment and therefore might guide decisions on who should receive this treatment. Rocconi et al. analyse gene expression data from patients with ovarian cancer receiving the autologous tumor cell immunotherapy gemogenovatucel-T (Vigil) as part of the VITAL study. The authors identify ENTPD1/CD39 expression as a predictor of relapse-free and overall survival benefit.