Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial

Rocconi, Rodney P.; Grosen, Elizabeth A.; Ghamande, Sharad; Chan, John K.; Barve, Minal; Oh, Jonathan; Tewari, Devansu; Morris, Peter C.; Stevens, Erin; Bottsford-Miller, Justin; Tang, Min; Aaron, Phylicia; Stanbery, Laura; Horvath, Staci; Wallraven, Gladice; Bognar, Ernest; Manning, Luisa; Nemunaitis, John; Shanahan, David; Slomovitz, Brian M.; Herzog, Thomas J.; Monk, Bradley J.; Coleman, Robert L.

doi:10.1016/s1470-2045(20)30533-7

Cited by 89 publications

(82 citation statements)

References 30 publications

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“…Preplanned subgroup analysis revealed a statistically significant advantage in BRCA1/2 wild-type patients who received Vigil versus placebo (HR 0.51 CI 0.30–0.88; p = 0.02) from randomization. Moreover, OS appeared improved in the BRCA1/2 wild-type Vigil treated patients compared to placebo (not reached vs. 41.4 months respectively; HR 0.49 90% CI 0.24–1.01; p = 0.049) [ 131 ]. Additionally, Vigil demonstrated efficacy in the homologous recombination population.…”

Section: Immune Therapy Clinical Trials In Ovarian Cancermentioning

confidence: 99%

Ovarian Cancer Immunotherapy and Personalized Medicine

Morand

Devanaboyina

Staats

et al. 2021

IJMS

Self Cite

209

118

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Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.

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Section: Immune Therapy Clinical Trials In Ovarian Cancermentioning

confidence: 99%

Ovarian Cancer Immunotherapy and Personalized Medicine

Morand

Devanaboyina

Staats

et al. 2021

IJMS

Self Cite

209

118

View full text Add to dashboard Cite

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“…Vigil (gemogenovatucel-T), using the same principle, is a vaccine based on the ex vivo transfection of autologous carcinoma cells with a short hairpin RNAi combined with the GM-CSF transgene targeting furin to downregulate TGF-β1 and TGF-β2 proteins. Clinical trials with Vigil also demonstrate a decrease in recurrence and improvement of survival rate, especially in ovarian cancer patients [ 119 ].…”

Section: Therapeutic Potential Of Inhibiting Tgf-β-related Emt In Carcinomamentioning

confidence: 99%

Harnessing Carcinoma Cell Plasticity Mediated by TGF-β Signaling

Wang

Thiery

2021

Cancers

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Epithelial cell plasticity, a hallmark of carcinoma progression, results in local and distant cancer dissemination. Carcinoma cell plasticity can be achieved through epithelial–mesenchymal transition (EMT), with cells positioned seemingly indiscriminately across the spectrum of EMT phenotypes. Different degrees of plasticity are achieved by transcriptional regulation and feedback-loops, which confer carcinoma cells with unique properties of tumor propagation and therapy resistance. Decoding the molecular and cellular basis of EMT in carcinoma should enable the discovery of new therapeutic strategies against cancer. In this review, we discuss the different attributes of plasticity in carcinoma and highlight the role of the canonical TGFβ receptor signaling pathway in the acquisition of plasticity. We emphasize the potential stochasticity of stemness in carcinoma in relation to plasticity and provide data from recent clinical trials that seek to target plasticity.

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“…Vigil also increases the number of CD3+CD8+ T cells in peripheral blood [125]. Phase II results in advanced ovarian cancer patients revealed improvement in both relapse free and overall survival in the BRCA wild type population [126]. This effect may be attributed to clonal neoantigen display via MHC II expression which is maximized in the BRCA wild type population due to intact homologous recombination compared to the BRCA mutant population [127].…”

Section: Synergistic Effects Of Angiogenesis Inhibitorsmentioning

confidence: 99%

Immune Response Role of Angiogenesis Inhibitors

Devanaboyina¹,

Ngo²,

Albalawy³

et al. 2021

COR

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Angiogenesis plays an important role in tumor growth. Established vasculature provides a supply of nutrients and other necessary survival factors for tumor cell maintenance. In addition, immune factors with capacity to both decrease immune activity leading to cancer suppression and to increase anticancer response are provided via VEGF stimulated angiogenesis. However, VEGF provides more than angiogenesis stimulation; it is itself a growth factor with activity to also decrease the stimulation of dendritic cells (DCs) and T cells involved in anti-cancer mechanisms. As such inhibition of VEGF provides immune therapeutic advantage. This was well demonstrated by IFN-ɣ ELISPOT assay in which T lymphocytes antitumor response was measured against multiple myeloma cells following exposure to myeloma lysate-loaded dendric cells. Block of VEGF lead to enhanced T lymphocyte anticancer immune response. Through stimulation of the immune system angiogenesis inhibitors can work in conjunction with immunotherapy, chemotherapy and/or radiation therapy. Recent clinical trials in advanced renal cell carcinoma, non-small cell lung cancer (NSCLC), and hepatocellular carcinoma have evidenced improved outcomes due to an immune enhancing effect with angiogenesis inhibition and in particular immune checkpoint blockade treatment.

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Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial

Cited by 89 publications

References 30 publications

Ovarian Cancer Immunotherapy and Personalized Medicine

Ovarian Cancer Immunotherapy and Personalized Medicine

Harnessing Carcinoma Cell Plasticity Mediated by TGF-β Signaling

Immune Response Role of Angiogenesis Inhibitors

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