Phase I Studies of Peptide Vaccine Cocktails Derived from GPC3, WDRPUH and NEIL3 for Advanced Hepatocellular Carcinoma

Ikeda, Masafumi; Okusaka, Takuji; Ohno, Izumi; Mitsunaga, Shuichi; Kondo, Shunsuke; Ueno, Hideki; Morizane, Chigusa; Gemmoto, Kazuto; Suna, Hideaki; Ushida, Yasunori; Furuse, Junji

doi:10.2217/imt-2020-0278

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…Some of the vaccine-based immunotherapy strategies include tumor-specific neoantigens vaccine, based on the so-called HEPAVAC project [ 39 , 40 ], as well as, peptide vaccines, like the glypican-3 (GPC3) vaccine, which is based on the overexpression of GPC3 on the tumor cell membrane in HCC. Based on the phase I study results, HCC patients that received this vaccine, expressed GPC3-specific cytotoxic T cells [ 41 , 42 ]. Another type of vaccine is the dendritic cells (DC) vaccine, which induces the elimination of tumor cells [ 43 , 44 ].…”

Section: Immunotherapy Strategies For Hccmentioning

confidence: 99%

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

Trifylli

Koustas

Papadopoulos³

et al. 2022

Life

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Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) constitute highly malignant forms of primary liver cancers. Hepatocellular and bile duct carcinogenesis is a multiplex process, caused by various genetic and epigenetic alterations, the influence of environmental factors, as well as the implication of the gut microbiome, which was undervalued in the previous years. The molecular and immunological analysis of the above malignancies, as well as the identification of the crucial role of intestinal microbiota for hepatic and biliary pathogenesis, opened the horizon for novel therapeutic strategies, such as immunotherapy, and enhanced the overall survival of cancer patients. Some of the immunotherapy strategies that are either clinically applied or under pre-clinical studies include monoclonal antibodies, immune checkpoint blockade, cancer vaccines, as well as the utilization of oncolytic viral vectors and Chimeric antigen, receptor-engineered T (CAR-T) cell therapy. In this current review, we will shed light on the recent therapeutic modalities for the above primary liver cancers, as well as on the methods for the enhancement and optimization of anti-tumor immunity.

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Section: Immunotherapy Strategies For Hccmentioning

confidence: 99%

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

Trifylli

Koustas

Papadopoulos³

et al. 2022

Life

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“…A significantly lower recurrence rate was detected in GPC3-positive patients treated both with surgery and vaccination compared to GPC3-positive patients that only underwent surgery [ 170 ]. A phase I study using two peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3, was carried out [ 171 ]. The two cocktails showed good tolerability, with 14 patients showing stable disease and some tumor regression [ 171 ].…”

Section: Glypican 3 As Targeting Proteinmentioning

confidence: 99%

“…A phase I study using two peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3, was carried out [ 171 ]. The two cocktails showed good tolerability, with 14 patients showing stable disease and some tumor regression [ 171 ].…”

Section: Glypican 3 As Targeting Proteinmentioning

confidence: 99%

Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies

Mossenta

Busato

et al. 2022

IJMS

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Hepatocellular carcinoma (HCC) is the second most lethal tumor, with a 5-year survival rate of 18%. Early stage HCC is potentially treatable by therapies with curative intent, whereas chemoembolization/radioembolization and systemic therapies are the only therapeutic options for intermediate or advanced HCC. Drug resistance is a critical obstacle in the treatment of HCC that could be overcome by the use of targeted nanoparticle-based therapies directed towards specific tumor-associated antigens (TAAs) to improve drug delivery. Glypican 3 (GPC3) is a member of the glypican family, heparan sulfate proteoglycans bound to the cell surface via a glycosylphosphatidylinositol anchor. The high levels of GPC3 detected in HCC and the absence or very low levels in normal and non-malignant liver make GPC3 a promising TAA candidate for targeted nanoparticle-based therapies. The use of nanoparticles conjugated with anti-GPC3 agents may improve drug delivery, leading to a reduction in severe side effects caused by chemotherapy and increased drug release at the tumor site. In this review, we describe the main clinical features of HCC and the common treatment approaches. We propose the proteoglycan GPC3 as a useful TAA for targeted therapies. Finally, we describe nanotechnology approaches for anti-GPC3 drug delivery systems based on NPs for HCC treatment.

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“…Recent developments focused on various ways to target liver cancer. We can mention the use of a peptide vaccine cocktail 67 with several antigens to increase the efficacy of antitumor response. The use of dendritic cells, an important platform for T cell activation, as vaccines has also demonstrated interesting results in several studies Table 3 .…”

Section: Development Of Cancer Vaccine For Hccmentioning

confidence: 99%

Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances

Charneau

Suzuki

Shimomura

et al. 2021

JHC

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Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. After surgery, up to 70% of patients experience relapses. The current first-line therapy for advanced cases of hepatocellular carcinoma (HCC) comprises sorafenib and lenvatinib administered as single-drug therapies. Regorafenib, cabozantinib, and ramucirumab are administered as second-line therapies. Recently, it has been reported that using the immune checkpoint inhibitors atezolizumab (anti-PDL1 antibody) and bevacizumab (anti-VEGF antibody) leads to longer overall survival of unresectable cases, when compared with the use of sorafenib. The role of cancer immunity against HCC has attracted the attention of clinicians. In this review, we describe our phase I/II clinical trials of peptide vaccines targeting GPC3 in HCC and discuss the potential of peptide vaccines targeting common cancer antigens that are highly expressed in HCC, such as WT-I, AFP, ROBO1, and FOXM1. Further, we introduce recent cancer vaccines targeting neoantigens, which have attracted attention in recent times, as well as present our preclinical studies, the results of which might aid to initiate a neoantigen vaccine clinical trial, which would be the first of its kind in Japan.

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Phase I Studies of Peptide Vaccine Cocktails Derived from GPC3, WDRPUH and NEIL3 for Advanced Hepatocellular Carcinoma

Cited by 18 publications

References 31 publications

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies

Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances

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