Gemogenovatucel-T (Vigil) maintenance immunotherapy: 3-year survival benefit in homologous recombination proficient (HRP) ovarian cancer

Walter, Adam; Rocconi, Rodney P.; Monk, Bradley J.; Herzog, Thomas J.; Manning, Luisa; Bognar, Ernest; Wallraven, Gladice; Aaron, Phylicia; Horvath, Staci; Tang, Min; Stanbery, Laura; Coleman, Robert L.; Nemunaitis, John

doi:10.1016/j.ygyno.2021.10.004

Cited by 15 publications

(20 citation statements)

References 34 publications

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“…Moreover, ad hoc analysis of a subset of 45 patients with homologous repair proficient (HRP) tumors by Myriad MyChoice CDx (Myriad Genetics, Salt Lake City, UT) also showed improvement in RFS and OS (HR = 0.39, p = 0.007 and HR = 0.34, p = 0.019, respectively) 6 . Long term follow-up confirmed a durable survival effect 7 . Three-year survival proportion from time of procurement was 83% for Vigil and 40% for placebo ( p = 0.0006) 7 .…”

Section: Introductionmentioning

confidence: 64%

“…Long term follow-up confirmed a durable survival effect 7 . Three-year survival proportion from time of procurement was 83% for Vigil and 40% for placebo ( p = 0.0006) 7 . A correlation of systemic immune response to Vigil clinical benefit was noted using ELISPOT assay 3 , 8 .…”

Section: Introductionmentioning

confidence: 64%

“…Previous analyses of Vigil relationship to BRCA1/2 -wt, HRP and TP53 mutation ( p53 -mu) subpopulations revealed correlation to clinical benefit 5 – 7 , 19 , 20 . These subpopulations were explored via KM analysis to assess the effect of combination biomarkers BRCA1/2 -wt, HRP, p53 -mu and genes identified as significant following multivariate analysis in this study on Vigil and placebo treatment effects as measured by OS and RFS.…”

Section: Methodsmentioning

confidence: 97%

“…Tissue is dissociated into cell suspension and cells are frozen at a concentration of 1.33 million cells/ml in freeze media (10% DMSO v/v in 1% HSA/plasma-Lyte A solution and stored long term in vapor phase nitrogen. Homologous recombination status [homologous recombination deficient (HRD) or HRP] was determined for all patients using the Myriad MyChoice CDx assay as previously described 6 , 7 . Patient demographics and CONSORT diagram are presented in Table 1 and Fig.…”

Section: Methodsmentioning

confidence: 99%

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

Rocconi

Stanbery²,

Tang³

et al. 2022

Commun Med

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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.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Rocconi

Stanbery²,

Tang³

et al. 2022

Commun Med

Self Cite

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show abstract

“…A clinical trial of an autologous tumor vaccine named gemogenovatucel-T (Vigil) (NCT02346747) has shown that Vigil provided personal neoantigens, downregulated TGF-β 1 and 2 and induced GMCSF expression, leading to systemic immunosuppressive activities. Current results have indicated long-term beneficial effects of Vigil with respect to primary endpoints and support further investigation of Vigil in ovarian cancer [ 110 ]. Studies have found that inhibiting the CXCR4/CXCL12 axis can increase sensitivity to anti-PD-1 and anti-CTLA4 immunological therapies [ 41 , 56 ].…”

Section: Therapeutic Prospective Of Cafs In Ovarian Cancermentioning

confidence: 67%

The Role of Cancer-Associated Fibroblasts in Ovarian Cancer

Zhang

Chen

Wang

et al. 2022

Cancers

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Ovarian cancer is a lethal gynecologic tumor and is generally resistant to conventional treatments. Stable cancer-associated fibroblasts (CAFs) are important cellular components in the ovarian cancer tumor microenvironment and may provide novel resources for future treatment strategies. Different subtypes of CAFs display specific functions in tumor pathogenesis and various CAF markers suggest potential treatment targets, such as FAP and GPR77. Both autocrine and paracrine cytokines play important roles in the CAF activation process and regulate tumor progression. Downstream mediators and pathways, including IL-6, TGF-β, NF-κB, mitogen-activated protein kinase (MAPK), and AKT/mTOR/(p70S6K), play important roles in the initiation, proliferation, invasiveness, and metastasis of ovarian cancer cells and also participate in angiogenesis, therapeutic resistance, and other biological processes. Several clinical or preclinical trials have targeted stromal fibroblasts and focused on the properties of CAFs to enhance ovarian cancer treatment outcomes. This review concentrates on the origins, subtypes, and activation of CAFs, as well as specific roles of CAFs in regulating tumor development and drug resistance, and aims to provide potential and prospective targets for improving the therapeutic efficacy of ovarian cancer treatment.

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A Scalable Engineered Extracellular Matrix Platform to Expand Tumor Cells

Moon

Neale

Kim

et al. 2023

Advanced NanoBiomed Research

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The demand for high‐throughput and scalable cell expansion platforms that can accommodate diverse cell types remains a critical requirement across various biomedical fields. Fibronectin (Fn), an essential component of the extracellular matrix (ECM), has been used as a conformal surface coating for two‐dimensional (2D) cell culture systems. However, the soluble, globular Fn used for 2D coatings differs structurally from the native Fn, which possesses a three‐dimensional (3D) fibrillar structure. Herein, a large‐scale engineered ECM (EECM) cell expansion platform based on a 3D fibrillar Fn network spanning over centimeters is presented. Extended fibrillar networks are formed by shearing dilute Fn solutions over tessellated polymeric scaffolds, which are conveniently prepared by 3D printing. The structure and size of the Fn‐based 3D EECM scaffold are optimized by evaluating the proliferation of a colorectal tumor cell line, CT26, commonly used in the in vivo tumor immunotherapy models. The 3D EECM scaffolds support a fourfold more efficient tumor cell expansion than a conventional 2D culture system, demonstrating the potential efficacy in supporting the robust expansion of cancer cells ex vivo with an eye on cancer immunotherapy.

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Gemogenovatucel-T (Vigil) maintenance immunotherapy: 3-year survival benefit in homologous recombination proficient (HRP) ovarian cancer

Cited by 15 publications

References 34 publications

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

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

The Role of Cancer-Associated Fibroblasts in Ovarian Cancer

A Scalable Engineered Extracellular Matrix Platform to Expand Tumor Cells

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