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  1. Article: Adoptive NK Cell Therapy: A Promising Treatment Prospect for Metastatic Melanoma.

    van Vliet, Amanda A / Georgoudaki, Anna-Maria / Raimo, Monica / de Gruijl, Tanja D / Spanholtz, Jan

    Cancers

    2021  Volume 13, Issue 18

    Abstract: Adoptive cell therapy (ACT) represents a promising alternative approach for patients with treatment-resistant metastatic melanoma. Lately, tumor infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor (CAR)-T cell therapy have shown improved ... ...

    Abstract Adoptive cell therapy (ACT) represents a promising alternative approach for patients with treatment-resistant metastatic melanoma. Lately, tumor infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor (CAR)-T cell therapy have shown improved clinical outcome, compared to conventional chemotherapy or immunotherapy. Nevertheless, they are limited by immune escape of the tumor, cytokine release syndrome, and manufacturing challenges of autologous therapies. Conversely, the clinical use of Natural Killer (NK) cells has demonstrated a favorable clinical safety profile with minimal toxicities, providing an encouraging treatment alternative. Unlike T cells, NK cells are activated, amongst other mechanisms, by the downregulation of HLA class I molecules, thereby overcoming the hurdle of tumor immune escape. However, impairment of NK cell function has been observed in melanoma patients, resulting in deteriorated natural defense. To overcome this limitation, "activated" autologous or allogeneic NK cells have been infused into melanoma patients in early clinical trials, showing encouraging clinical benefit. Furthermore, as several NK cell-based therapeutics are being developed for different cancers, an emerging variety of approaches to increase migration and infiltration of adoptively transferred NK cells towards solid tumors is under preclinical investigation. These developments point to adoptive NK cell therapy as a highly promising treatment for metastatic melanoma in the future.
    Language English
    Publishing date 2021-09-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13184722
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34

    van Vliet, Amanda A / Peters, Ella / Vodegel, Denise / Steenmans, Daniëlle / Raimo, Monica / Gibbs, Susan / de Gruijl, Tanja D / Duru, Adil D / Spanholtz, Jan / Georgoudaki, Anna-Maria

    iScience

    2023  Volume 26, Issue 7, Page(s) 107078

    Abstract: Umbilical cord blood (UCB) ... ...

    Abstract Umbilical cord blood (UCB) CD34
    Language English
    Publishing date 2023-06-09
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.107078
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer.

    Toffoli, Elisa C / van Vliet, Amanda A / Verheul, Henk W M / van der Vliet, Hans J / Tuynman, Jurriaan / Spanholtz, Jan / de Gruijl, Tanja D

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 12

    Abstract: Introduction: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft- ... ...

    Abstract Introduction: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required. In this study, we analyzed the effects of an allogeneic off-the-shelf NK cell product, on the tumor microenvironment (TME) of primary and metastatic colorectal cancer (pCRC and mCRC, respectively). Moreover, we explored if the combination of NK cells with R848, a toll-like receptors 7/8 ligand, could further enhance any pro-inflammatory effects.
    Methods: Ex vivo expanded umbilical cord blood stem cell derived NK cells were co-cultured with pCRC or mCRC single-cell suspensions in the presence or absence of R848 for 5 days, during and after which flow cytometry and cytokine release profiling were performed.
    Results: NK cells efficiently induced lysis of tumor cells in both pCRC and mCRC single-cell suspensions and thereby controlled growth rates during culture. They also induced differentiation of infiltrating monocytic cells to an activated DC phenotype. Importantly, this NK-mediated myeloid conversion was also apparent in cultures after tumor cell depletion and was further enhanced by combining NK cells with R848. Moreover, NK cells, and to a greater extent, the combination of NK cells and R848, triggered CD8
    Conclusion: Allogeneic NK cells engaged in favorable myeloid crosstalk, displayed effective antitumor activity and, when combined with R848, induced a pro-inflammatory shift of the CRC TME. These findings prompt the investigation of NK cells and R848 as a combination therapy for solid tumors.
    MeSH term(s) Humans ; Monocytes ; Dendritic Cells ; Killer Cells, Natural ; Interleukin-12/pharmacology ; Colorectal Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation ; Tumor Microenvironment
    Chemical Substances Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2023-12-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-007554
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor.

    Toffoli, Elisa C / Sheikhi, Abdolkarim / Lameris, Roeland / King, Lisa A / van Vliet, Amanda / Walcheck, Bruce / Verheul, Henk M W / Spanholtz, Jan / Tuynman, Jurriaan / de Gruijl, Tanja D / van der Vliet, Hans J

    Cancers

    2021  Volume 13, Issue 21

    Abstract: The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor ... ...

    Abstract The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.
    Language English
    Publishing date 2021-10-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13215446
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Boosting Natural Killer Cell Therapies in Glioblastoma Multiforme Using Supramolecular Cationic Inhibitors of Heat Shock Protein 90.

    Saha, Tanmoy / van Vliet, Amanda A / Cui, Chunxiao / Macias, Jorge Jimenez / Kulkarni, Arpita / Pham, Luu Nhat / Lawler, Sean / Spanholtz, Jan / Georgoudaki, Anna-Maria / Duru, Adil Doganay / Goldman, Aaron

    Frontiers in molecular biosciences

    2021  Volume 8, Page(s) 754443

    Abstract: Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for ... ...

    Abstract Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood-brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids,
    Language English
    Publishing date 2021-12-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2021.754443
    Database MEDical Literature Analysis and Retrieval System OnLINE

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