A pilot study of tremelimumab – a monoclonal antibody against CTLA-4 – in combination with either trans catheter arterial chemoembolization (TACE) or radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).

Duffy, Austin G.; Makarova-Rusher, Oxana V.; Kerkar, Sid P.; Kleiner, David E.; Fioravanti, Suzanne; Walker, Melissa; Carey, Stephanie; Figg, William D.; Steinberg, Seth M.; Anderson, Victoria; Abi-Jaoudeh, Nadine; Levi, Elliot; Wood, Bradford J.; Greten, Tim F.

doi:10.1200/jco.2015.33.15_suppl.4081

Cited by 17 publications

(10 citation statements)

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“…However, in patients with spontaneous tumor-specific T cell responses, the function of these T cells is impaired, but their activation could be enhanced in vitro by administration of anti-CTLA-4 antibodies (Mizukoshi, et al, 2011). ‘Checkpoint-inhibitors’ are therefore plausible treatment approaches in HCC patients and are currently evaluated in clinical trials using the anti-CTLA-4 antibody (Duffy AG, et al, 2015; Sangro, et al, 2013). …”

Section: Cells Of the Hepatic Tumor Environment And Their Regulatimentioning

confidence: 99%

“…Anti-CTLA-4 antibodies do not only disinhibit CTL, but also restrain the suppressive abilities of CTLA-4 expressing T reg. Blockade of CTLA-4 on both T cell subsets contributes to the anti-tumor activity (Peggs, et al, 2009) and could potentially lead to enhanced anti-tumor T cell responses in patients with HCC (Duffy AG, et al, 2015). Other approaches to target T reg, of which only a few are mentioned here, include low-dose cyclophosphamide administration (Greten, et al, 2010) and toll-like receptor stimulation (Nishikawa, et al, 2006; Y.…”

Section: Cells Of the Hepatic Tumor Environment And Their Regulatimentioning

confidence: 99%

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Tumor regulation of the tissue environment in the liver

Eggert

Greten

2017

Pharmacology & Therapeutics

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The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses. In this review, we characterize cells of the TME with pro- and anti-tumor function in primary and metastatic liver tumors. Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic approaches targeting the TME could unleash tumor-specific immune responses to improve survival of liver cancer patients.

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Section: Cells Of the Hepatic Tumor Environment And Their Regulatimentioning

confidence: 99%

Section: Cells Of the Hepatic Tumor Environment And Their Regulatimentioning

confidence: 99%

Tumor regulation of the tissue environment in the liver

Eggert

Greten

2017

Pharmacology & Therapeutics

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“…Checkpoint inhibitors have revolutionized cancer care and have been proven to lead to durable tumor shrinkage in a subset of patients that has translated into significant OS advantages over standard therapy in several cancer types . To our knowledge to date, interference with the CTLA‐4‐CD80/86 and PD‐1/PD‐L1 axis has shown promise in patients with HCC and many clinical trials using this approach have been reported or currently are underway (Table ) …”

Section: Introductionmentioning

confidence: 99%

“…One area of concern was the relatively high rate of grade 3 and grade 4 (Common Terminology Criteria for Adverse Events version 4) transaminitis (45%), although this adverse event was reversible, did not progress to liver failure, and was not clearly immune mediated in that no patient needed immunosuppression for recovery. Importantly, results of studies of tremelimumab, clinical anecdotes, and a pilot study in patients with viral hepatitis have indicated that immune checkpoint blockade is safe in the setting of chronic viral infection, and may have antiviral activity. Sangro et al demonstrated a decrease of >200‐fold in serum HCV viral load at day 210 in 12 patients treated with tremelimumab; in 3 patients there was a transient complete viral response .…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in hepatocellular carcinoma: Primed to make a difference?

Harding

Dika

Abou‐Alfa

2015

Cancer

113

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Page 1 of 27 CancerThis is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version record. Please cite this article as doi:10.1002/cncr.29769.This article is protected by copyright. All rights reserved. Accepted ArticleABSTRACT Advanced hepatocellular carcinoma (HCC) carries a dismal prognosis and the current treatment is limited to sorafenib, an agent with modest benefit. Preclinical data indicate that several immunologic mechanisms are at play to promote HCC development and growth while impairing effective antitumor immune surveillance. Several novel approaches geared at manipulating the immune response to HCC have suggested a therapeutic benefit in early stage clinical trials, indicating a real potential to augment tumor-specific immunity and improve outcomes in this disease. Herein, we review the barriers to an effective immune response against HCC and contemporary clinical investigations that may be "primed"to alter the natural history of HCC.

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“…Such alterations were associated with a tumor necrosis rate of 950 % and improved clinical outcome. Tremelimumab appears to be feasible with TACE and other locoregional therapies, but more data are required to fully assess the safety of this approach (NCT01853618) [105]. Data from this small series indicated a high response rate (40 %) for extra-hepatic disease, perhaps supporting the hypothesis of a synergistic anti-tumor response.…”

Section: Combination Approach Of Locoregional and Systemic Therapiesmentioning

confidence: 91%

Advanced Hepatocellular Cancer: the Current State of Future Research

Connell

Harding

Abou‐Alfa

2016

Curr. Treat. Options in Oncol.

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Hepatocellular carcinoma is a common malignancy worldwide, rapidly rising in incidence. While there have been some developments in advancing therapeutic options in this disease, these have admittedly been modest to date, and as a result, this is a patient population with an inherently poor prognosis. Currently, sorafenib remains the only established systemic therapy proven to increase the overall survival of patients with advanced disease. The approval of sorafenib in 2007 ushered in the era of targeted therapies. Several phase 2 and 3 clinical trials have failed however to improve on sorafenib in the first-line setting, and no single agent has been demonstrated to impact outcomes after sorafenib failure. Having reached somewhat of an impasse in terms of drug development in hepatocellular carcinoma, enthusiasm in the field has moved toward innovative approaches such as molecular characterization and immunotherapy in an attempt to impact survival. This review highlights the current endeavors in terms of experimental research for patients with advanced hepatocellular carcinoma.

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A pilot study of tremelimumab – a monoclonal antibody against CTLA-4 – in combination with either trans catheter arterial chemoembolization (TACE) or radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).

Cited by 17 publications

References 0 publications

Tumor regulation of the tissue environment in the liver

Tumor regulation of the tissue environment in the liver

Immunotherapy in hepatocellular carcinoma: Primed to make a difference?

Advanced Hepatocellular Cancer: the Current State of Future Research

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