For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
48
references
 Top references
cited by
48
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      457
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK) therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR-) specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92) against renal cell carcinoma (RCC) cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

          Related collections

          Most cited references48

          • Record: found
          • Abstract: found
          • Article: not found

          Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

          Christine E. Brown, Darya Alizadeh, Renate Starr … (2016)
          A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).
          Article 0 comments Cited 733 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells.

            J H Gong, G Maki, H G Klingemann (1994)
            The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
            Article 0 comments Cited 200 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              CS1-Specific Chimeric Antigen Receptor (CAR)-Engineered Natural Killer Cells Enhance In Vitro and In Vivo Anti-tumor Activity Against Human Multiple Myeloma

              Jianhong Chu, Youcai Deng, Don Benson … (2013)
              Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successful in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro, CS1-CAR NK cells displayed enhanced MM cytolysis and IFN-γ production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo, CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM.
              Article 0 comments Cited 185 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Huizhong Li:
                ORCID: http://orcid.org/0000-0003-4241-8109
                Junnian Zheng:
                ORCID: http://orcid.org/0000-0003-0208-6410
                Journal
                Journal ID (nlm-ta): J Immunol Res
                Journal ID (iso-abbrev): J Immunol Res
                Journal ID (publisher-id): JIR
                Title: Journal of Immunology Research
                Publisher: Hindawi
                ISSN (Print): 2314-8861
                ISSN (Electronic): 2314-7156
                Publication date (Print): 2017
                Publication date (Electronic): 20 December 2017
                Volume: 2017
                Electronic Location Identifier: 6915912
                Affiliations
                1Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
                2Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, China
                3Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China
                Author notes

                Academic Editor: Rosa Molfetta

                Author information
                http://orcid.org/0000-0001-6871-3435
                http://orcid.org/0000-0003-4241-8109
                http://orcid.org/0000-0003-0208-6410
                Article
                DOI: 10.1155/2017/6915912
                PMC ID: 5750507
                PubMed ID: 29423418
                SO-VID: 15e49f3c-4b84-4d91-905c-4d69ea0aed15
                Copyright © Copyright © 2017 Qing Zhang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 August 2017
                Date revision received : 17 September 2017
                Date accepted : 8 October 2017
                Funding
                Funded by: Shandong Provincial Natural Science Foundation
                Award ID: ZR2015JL027
                Funded by: Natural Science Foundation of Jiangsu Province
                Award ID: BK20161157
                Award ID: BK2012146
                Funded by: Jiangsu Province Social Development Key Projects
                Award ID: BE2016643
                Funded by: National Natural Science Foundation of China
                Award ID: 81301946
                Categories
                Subject: Research Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content457

                See all similar

                Cited by45

                See all cited by

                Most referenced authors785

                See all reference authors