Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

Rochigneux, Philippe; Chanez, Brice; Rauglaudre, Bernadette de; Mitry, Emmanuel; Chabannon, Christian; Gilabert, Marine

doi:10.3390/cancers13020271

Cited by 48 publications

(35 citation statements)

References 129 publications

(72 reference statements)

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“…In summary, the most promising efforts in developing immune cell therapies to treat and cure liver diseases have been reported for the treatment of HCC. Several clinical phase I/II studies are currently ongoing, with most of them investigating the potential of CAR-T cell therapies [ 142 ].…”

Section: Cellular Therapies For Treatment Of Liver Diseases and Induction Of Regenerationmentioning

confidence: 99%

Cell-Based Regeneration and Treatment of Liver Diseases

Hofmann

Hackl

Esser

et al. 2021

IJMS

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The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function.

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Section: Cellular Therapies For Treatment Of Liver Diseases and Induction Of Regenerationmentioning

confidence: 99%

Cell-Based Regeneration and Treatment of Liver Diseases

Hofmann

Hackl

Esser

et al. 2021

IJMS

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“…One phase I study, that is applicable to HLA-A2 + patients, utilizes autologous genetically modified AFP c332 T cells for the treatment of HCC (NCT03132792). First promising results have already been presented (overview for this and other ACT/HCC studies in [ 132 ]). In this clinical study, targeting AFP + HCC tumors with AFP-specific CAR-T cells resulted in one complete response out of four patients and one patient had a partial response with 100% reduction of targeted tumors and only one non-targeted tumor nodule remained at therapy week eight.…”

Section: Other Immunotherapeutic Approaches Of Hccmentioning

confidence: 99%

Prospects and Challenges for T Cell-Based Therapies of HCC

Woller

Engelskircher

Wirth

et al. 2021

Cells

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The scope of therapeutic options for the treatment of hepatocellular carcinoma (HCC) has recently been expanded by immunotherapeutic regimens. T cell-based therapies, especially in combination with other treatments have achieved far better outcomes compared to conventional treatments alone. However, there is an emerging body of evidence that eliciting T cell responses in immunotherapeutic approaches is insufficient for favorable outcomes. Immune responses in HCC are frequently attenuated in the tumor microenvironment (TME) or may even support tumor progress. Hence, therapies with immune checkpoint inhibitors or adoptive cell therapies appear to necessitate additional modification of the TME to unlock their full potential. In this review, we focus on immunotherapeutic strategies, underlying molecular mechanisms of CD8 T cell immunity, and causes of treatment failure in HCC of viral and non-viral origin. Furthermore, we provide an overview of TME features in underlying etiologies of HCC patients that mediate therapy resistance to checkpoint inhibition and discuss strategies from the literature concerning current approaches to these challenges.

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“…ACT refers to a method of passive immunotherapy in which immune cells with tumor-killing effects are expanded and cultured in vitro , and then returned to tumor patients to achieve anti-tumor purposes[ 44 ]. ACT mainly includes cytokine-induced killer cell (CIK), natural killer (NK) cell, tumor-infiltrating lymphocyte, T cell receptor-engineered T cell, and chimeric antigen receptor T cell (CAR-T) therapy[ 18 , 44 , 45 ]. Twenty years ago, Takayama et al [ 46 ] conducted a RCT study in which 150 patients who had undergone curative resection for HCC were allocated to no adjuvant treatment ( n = 74) or adoptive immunotherapy ( n = 76).…”

Section: Immunotherapymentioning

confidence: 99%

Thermal ablation and immunotherapy for hepatocellular carcinoma: Recent advances and future directions

Bo¹,

Sun²,

Yu³

et al. 2021

WJGO

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Hepatocellular carcinoma (HCC) is one of most common cancers that cause death in the world. Thermal ablation (TA) is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation. Particularly for small and early HCCs, TA can be considered as the first-line curative treatment. However, local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly. Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients, which has the potential to reduce the tumor recurrence and metastasis. The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence. Herein we summarize the latest progress in TA, immunotherapy, and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

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Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials

Cited by 48 publications

References 129 publications

Cell-Based Regeneration and Treatment of Liver Diseases

Cell-Based Regeneration and Treatment of Liver Diseases

Prospects and Challenges for T Cell-Based Therapies of HCC

Thermal ablation and immunotherapy for hepatocellular carcinoma: Recent advances and future directions

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