Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors

Jan, Chia-Ing; Huang, Shi-Wei; Canoll, Peter; Bruce, Jeffrey N.; Lin, Yu-Chuan; Pan, Chih‐Ming; Lu, Hsin‐Man; Chiu, Shao‐Chih; Cho, Der Yang

doi:10.1136/jitc-2021-003050

Cited by 48 publications

(40 citation statements)

References 65 publications

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“…In addition, it has been reported that PD-L1-CAR-NK cells with PRDX1 overexpression display a potent antitumor activity against breast cancer cells under oxidative stress ( 126 ). HLA-G CAR-NK cells present an effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro , as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models ( 127 ). A preclinical report demonstrated that the tissue factor (TF)-CAR-NK cells alone could kill TNBC cells and their efficacy were enhanced with L-ICON ADCC in vitro ( 128 ).…”

Section: Adoptive Cell Transfer–based Therapymentioning

confidence: 99%

Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer

Luo

Wang

et al. 2022

Front. Oncol.

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Breast cancer is the most commonly diagnosed cancer (estimated 2.3 million new cases in 2020) and the leading cause of cancer death (estimated 685,000 deaths in 2020) in women globally. Breast cancers have been categorized into four major molecular subtypes based on the immunohistochemistry (IHC) expression of classic hormone and growth factor receptors including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as a proliferation marker Ki-67 protein expression. Triple-negative breast cancer (TNBC), a breast cancer subtype lacking ER, PR, and HER2 expression, is associated with a high metastatic potential and poor prognosis. TNBC accounts for approximately only 15%–20% of new breast cancer diagnoses; it is responsible for most breast cancer–related deaths due to the lack of targeted treatment options for this patient population, and currently, systemic chemotherapy, radiation, and surgical excision remain the major treatment modalities for these patients with TNBC. Although breast cancer patients in general do not have a robust response to the immunotherapy, a subset of TNBC has been demonstrated to have high tumor mutation burden and high tumor-infiltrating lymphocytes, resembling the features observed on melanoma or lung cancers, which can benefit from the treatment of immune checkpoint inhibitors (ICIs). Therefore, the immunogenic nature of this aggressive disease has presented an opportunity for the development of TNBC-targeting immunotherapies. The recent US Food and Drug Administration approval of atezolizumab in combination with the chemotherapeutic agent nab-paclitaxel for the treatment of PD-L1-positive unresectable, locally advanced, or metastatic TNBC has led to a new era of immunotherapy in TNBC treatment. In addition, immunotherapy becomes an active research area, both in the cancer biology field and in the oncology field. In this review, we will extend our coverage on recent discoveries in preclinical research and early results in clinical trials from immune molecule-based therapy including cytokines, monoclonal antibodies, antibody–drug conjugates, bi-specific or tri-specific antibodies, ICIs, and neoantigen cancer vaccines; oncolytic virus-based therapies and adoptive immune cell transfer–based therapies including TIL, chimeric antigen receptor-T (CAR-T), CAR-NK, CAR-M, and T-cell receptor-T. In the end, we will list a series of the challenges and opportunities in immunotherapy prospectively and reveal novel technologies such as high-throughput single-cell sequencing and CRISPR gene editing-based screening to generate new knowledges of immunotherapy.

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Section: Adoptive Cell Transfer–based Therapymentioning

confidence: 99%

Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer

Luo

Wang

et al. 2022

Front. Oncol.

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“…Jan et al developed CAR-NK cells targeting HLA-G and evaluated the synergy of CAR-NK cells combined with low-dose chemotherapy (116). Their study showed that pretreatment with low-dose chemotherapy can induce the overexpression of HLA-G, thus enhancing the antitumor cytotoxicity of HLA-G-CAR-NK cells (91).…”

Section: Ovarian Cancermentioning

confidence: 99%

Preclinical and clinical studies of CAR-NK-cell therapies for malignancies

Song

et al. 2022

Front. Immunol.

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The development of chimeric antigen receptor T (CAR-T) cell therapy, a specific type of immunotherapy, in recent decades was a fantastic breakthrough for the treatment of hematological malignancies. However, difficulties in collecting normal T cells from patients and the time cost of manufacturing CAR-T cells have limited the application of CAR-T-cell therapy. In addition, the termination of related clinical trials on universal CAR-T cell therapy has made further research more difficult. Natural killer (NK) cells have drawn great attention in recent years. Chimeric antigen receptor-NK (CAR-NK) cell therapy is a promising strategy in the treatment of malignant tumors because of its lack of potential for causing graft-versus-host disease (GVHD). In this review, we will address the advances in and achievements of CAR-NK cell therapy.

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“…by overexpression of HLA-G regulatory miRs (63), by HLA-G-specific CRISPR/Cas9 systems (125) or by simple inhibition of HLA-G with antibodies (96), resulted in an increased lysis of tumor cells by immune effector cells. Recently, also chimeric antigen receptors (CARs) directed against HLA-G have been published (126).…”

Section: Role Of Hla-g For Cancer Immunotherapymentioning

confidence: 99%

The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors

et al. 2022

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The non-classical human leukocyte antigen G (HLA-G) is a potent regulatory protein involved in the induction of immunological tolerance. This is based on the binding of membrane-bound as well as soluble HLA-G to inhibitory receptors expressed on various immune effector cells, in particular NK cells and T cells, leading to their attenuated functions. Despite its restricted expression on immune-privileged tissues under physiological conditions, HLA-G expression has been frequently detected in solid and hematopoietic malignancies including urological cancers, such as renal cell and urothelial bladder carcinoma and has been associated with progression of urological cancers and poor outcome of patients: HLA-G expression protects tumor cells from anti-tumor immunity upon interaction with its inhibitory receptors by modulating both the phenotype and function of immune cells leading to immune evasion. This review will discuss the expression, regulation, functional and clinical relevance of HLA-G expression in urological tumors as well as its use as a putative biomarker and/or potential therapeutic target for the treatment of renal cell carcinoma as well as urothelial bladder cancer.

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Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors

Cited by 48 publications

References 65 publications

Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer

Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer

Preclinical and clinical studies of CAR-NK-cell therapies for malignancies

The Human Leukocyte Antigen G as an Immune Escape Mechanism and Novel Therapeutic Target in Urological Tumors

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