The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture

Hoh, Alexander; Dewerth, Alexander; Vogt, Fabian; Wenz, Julia; Baeuerle, Patrick A.; Warmann, Steven W.; Fuchs, Joerg; Armeanu–Ebinger, Sorin

doi:10.1111/liv.12011

Cited by 44 publications

(30 citation statements)

References 47 publications

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“…In a recent study (63), γδ T-cells expanded ex vivo with an aminobisphosphonate were able to recognize and lyse HCC cell lines in co-culture assays – thus, providing the rationale for targeted immunotherapy in patients with HCC in the future.…”

Section: γδ T-cells and Hepatitismentioning

confidence: 99%

Gamma Delta T-lymphocytes in Hepatitis C and Chronic Liver Disease

et al. 2014

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Discovered 30 years ago, gamma delta (γδ) T-lymphocytes remain an intriguing and enigmatic T-cell subset. Although in humans they comprise a small fraction of the total circulating T-lymphocyte pool, they represent an important T-cell subset in tissues such as the liver, with roles bridging the innate and adaptive immune systems. The associations of γδ T-lymphocytes with chronic liver disease have been explored – however, there remain conflicting data as to whether these T-cells are pathogenic or protective. In patients with some forms of liver disease, their expansion in the periphery and especially in the liver may indeed help pathogen clearance, while in other conditions their presence may, in contrast, contribute to disease progression. γδ T-cells can also express CD161, a C-type lectin, and such cells have been found to be involved in the pathogenesis of inflammatory disease. CD161+ T-cells of diverse subsets are known to be enriched in the livers of patients with chronic hepatitis C. This article serves to provide a review of the γδ T-cell population and its role in hepatitis C and other chronic liver diseases, and also explores a potential role of the CD161+ γδ T-cells in liver diseases.

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Section: γδ T-cells and Hepatitismentioning

confidence: 99%

Gamma Delta T-lymphocytes in Hepatitis C and Chronic Liver Disease

et al. 2014

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“…Alendronate (ALD), is a nitrogen containing bisphosphonate (N-BP) that can sensitise tumour cells to killing by Vγ9Vδ2 T cells in both in vitro [15], [16], [17], [18], [19] and in vivo studies [20], [21], [22], [23], [24], [25], [26], [27]. The encapsulation of ALD in liposomes (L-ALD), has been shown to increase its therapeutic efficacy [24].…”

Section: Introductionmentioning

confidence: 99%

Investigating in vitro and in vivo αvβ6 integrin receptor-targeting liposomal alendronate for combinatory γδ T cell immunotherapy

Hodgins

Al-Jamal

Wang

et al. 2017

Journal of Controlled Release

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The αvβ6 integrin receptor has been shown to be overexpressed on many types of cancer cells, resulting in a more pro-invasive and aggressive phenotype, this makes it an attractive target for selective drug delivery. In tumours that over-express the αvβ6 receptor, cellular uptake of liposomes can be enhanced using ligand-targeted liposomes. It has previously been shown in both in vitro and in vivo studies that liposomal alendronate (L-ALD) can sensitise cancer cells to destruction by Vγ9Vδ2 T cells. It is hypothesised that by using the αvβ6-specific peptide A20FMDV2 as a targeting moiety for L-ALD, the therapeutic efficacy of this therapy can be increased in αvβ6 positive tumours. Targeted liposomes (t-L) were formulated and the targeting efficacy of targeted liposomes (t-L) was assessed by cell uptake and cytotoxicity studies in the αvβ6 positive cells line A375Pβ6. Bio-distribution of both L and t-L were carried out in αvβ6 positive (A375Pβ6 and PANC0403) and αvβ6 negative (A375Ppuro and PANC-1) subcutaneous tumour mouse models. Immuno-compromised mice bearing A375Pβ6 experimental metastatic lung tumours were treated with L-ALD or t-L-ALD as monotherapies or in combination with ex vivo-expanded Vγ9Vδ2 T cells. In vitro, αvβ6-dependant uptake of t-L was observed, with t-L-ALD being more effective than L-ALD at sensitising A375Pβ6 to γδ T cells. Interestingly, t-L-ALD led to slightly higher but not significant reduction in tumour growth compared to L-ALD, when used as monotherapy in vivo. Moreover, both L-ALD and t-L-ALD led to significant reductions in tumour growth when used in combination with γδ T cells in vivo but t-L-ALD offered no added advantage compared to L-ALD.

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“…The purity of γδ T cells after negative MACS isolation, as estimated by flow cytometry using an anti-TCRγδ-PE antibody (Miltenyi Biotech), was > 99%. To expand γδ T cells, PBMCs were plated on plastic culture dishes in RPMI-1640 medium supplemented with 10% FCS, 1% L-glutamine and 1% penicillin/streptomycin, as previously described 39 . After MACS isolation, γδ T cells were either cultured for another 4 d or immediately frozen and cryopreserved in liquid nitrogen for 4 mo.…”

Section: Methodsmentioning

confidence: 99%

Targeting EpCAM (CD326) for immunotherapy in hepatoblastoma

et al. 2013

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Hepatoblastoma (HB) is the most common liver cancer in children. Recurrence of HB after chemotherapy and surgery is frequent among high-risk patients and is associated with chemoresistance. Immunotherapy may improve poor treatment outcomes in HB patients. Cytotoxic leukocytes of the innate and adaptive immune system including different populations of cytotoxic T cells play a major role in fighting developing tumors. In this setting, monoclonal antibodies may be employed to specifically direct immune responses toward tumor cells. We addressed this issue by using humanized antibodies that recognize the cell surface molecule EpCAM (CD326, overexpressed in hepatic tumor cells) to enhance immune responses against HB. EpCAM was constantly expressed on HB cells and its expression was independent of previous therapy based on the DNA-damaging agent cisplatin. Co-culture assays performed with two well-described HB cell lines and tumor tissue cultures demonstrated that tumor cell lysis by γδ T cells can be dramatically augmented by applying EpCAM-specific monoclonal antibodies. These data emphasize the value of antitumor immune responses and encourage adapting immunotherapeutic regimens to improve the outcome of high risk HB.

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The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture

Abstract: Bispecific antibodies such as MT110 might be used to intensify the antitumoural effect of γδ T cells in context of adoptive immune cell transfer. Optimised immunotherapeutic strategies might therefore improve the outcome of high risk hepatoblastoma and hepatocellular carcinoma.

Cited by 44 publications

References 47 publications

Gamma Delta T-lymphocytes in Hepatitis C and Chronic Liver Disease

Gamma Delta T-lymphocytes in Hepatitis C and Chronic Liver Disease

Investigating in vitro and in vivo αvβ6 integrin receptor-targeting liposomal alendronate for combinatory γδ T cell immunotherapy

Targeting EpCAM (CD326) for immunotherapy in hepatoblastoma

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