Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

Parlar, Ayhan; Sayitoğlu, Ece Canan; Özkazanç, Didem; Georgoudaki, Anna‐Maria; Pamukcu, Cevriye; Aras, Mertkaya; Josey, Benjamin J.; Chrobok, Michael; Branecki, Suzanne; Zahedimaram, Pegah; Ikromzoda, Lolai; Alici, Evren; Erman, Batu; Duru, Adil Doğanay; Sütlü, Tolga

doi:10.1002/eji.201948140

Cited by 37 publications

(33 citation statements)

References 57 publications

(73 reference statements)

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“…Additionally, as a new angle to introduce antigen-specific recognition to NK cells, we and others recently published a novel approach to arm an NK cell line with a TCR in order to target tumors with high specificity while at the same time overcoming the problem of endogenous TCR mispairing (56,57). Combining expression of antigen-specific receptors and tumor-specific NK cell receptors to further enhance anti-tumor responses by dual arming stands out as one of the future reflections of this study.…”

Section: Discussionmentioning

confidence: 99%

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

et al. 2020

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Sayitoglu et al. Boosting NK Cell-Mediated Sarcoma Targeting cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1 + or NKG2D + GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.

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Section: Discussionmentioning

confidence: 99%

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

et al. 2020

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“…Similarly, another study [ 118 ] demonstrated that ectopic expression of αβ TCR in NK92 and YTS NK cells along with CD3 subunits induces the expression of a functional antigen-specific TCR against the HLA-A2 restricted tyrosinasi-derived melanoma epitope Tyr 368–377 . Most importantly, these cells showed anti-tumor killing capabilities against melanoma cells both in vitro and in vivo.…”

Section: Nk Cell Engineering Strategiesmentioning

confidence: 89%

Engineering the Bridge between Innate and Adaptive Immunity for Cancer Immunotherapy: Focus on γδ T and NK Cells

Morandi

Yazdanifar

Cocco

et al. 2020

Cells

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Most studies on genetic engineering technologies for cancer immunotherapy based on allogeneic donors have focused on adaptive immunity. However, the main limitation of such approaches is that they can lead to severe graft-versus-host disease (GvHD). An alternative approach would bolster innate immunity by relying on the natural tropism of some subsets of the innate immune system, such as γδ T and natural killer (NK) cells, for the tumor microenvironment and their ability to kill in a major histocompatibility complex (MHC)-independent manner. γδ T and NK cells have the unique ability to bridge innate and adaptive immunity while responding to a broad range of tumors. Considering these properties, γδ T and NK cells represent ideal sources for developing allogeneic cell therapies. Recently, significant efforts have been made to exploit the intrinsic anti-tumor capacity of these cells for treating hematologic and solid malignancies using genetic engineering approaches such as chimeric antigen receptor (CAR) and T cell receptor (TCR). Here, we review over 30 studies on these two approaches that use γδ T and NK cells in adoptive cell therapy (ACT) for treating cancer. Based on those studies, we propose several promising strategies to optimize the clinical translation of these approaches.

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“…Beyond normal T lymphocytes, several other cell types can also be equipped with a TCR for neoantigen targeting and offer special advantages. TCR-transduced NK cells retain their natural cytotoxicity in addition to the newly-acquired MHC-restricted capabilities, and are therefore resistant to HLA-loss, which is a main mechanism of tumor evasion under TCR therapy [ 96 , 97 , 98 ]. Induced pluripotent stem cells (iPS) can be used to transform derived lymphocytes or other mesenchymal cells to cytotoxic T cells of any specificity with extended proliferative potential [ 99 ].…”

Section: Critical Tasksmentioning

confidence: 99%

Breaking Bottlenecks for the TCR Therapy of Cancer

Gaissmaier

Elshiaty

Christopoulos

2020

Cells

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Immune checkpoint inhibitors have redefined the treatment of cancer, but their efficacy depends critically on the presence of sufficient tumor-specific lymphocytes, and cellular immunotherapies develop rapidly to fill this gap. The paucity of suitable extracellular and tumor-associated antigens in solid cancers necessitates the use of neoantigen-directed T-cell-receptor (TCR)-engineered cells, while prevention of tumor evasion requires combined targeting of multiple neoepitopes. These can be currently identified within 2 weeks by combining cutting-edge next-generation sequencing with bioinformatic pipelines and used to select tumor-reactive TCRs in a high-throughput manner for expeditious scalable non-viral gene editing of autologous or allogeneic lymphocytes. “Young” cells with a naive, memory stem or central memory phenotype can be additionally armored with “next-generation” features against exhaustion and the immunosuppressive tumor microenvironment, where they wander after reinfusion to attack heavily pretreated and hitherto hopeless neoplasms. Facilitated by major technological breakthroughs in critical manufacturing steps, based on a solid preclinical rationale, and backed by rapidly accumulating evidence, TCR therapies break one bottleneck after the other and hold the promise to become the next immuno-oncological revolution.

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Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer

Cited by 37 publications

References 57 publications

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

Boosting Natural Killer Cell-Mediated Targeting of Sarcoma Through DNAM-1 and NKG2D

Engineering the Bridge between Innate and Adaptive Immunity for Cancer Immunotherapy: Focus on γδ T and NK Cells

Breaking Bottlenecks for the TCR Therapy of Cancer

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