Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
February-2019 Volume 17 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2019 Volume 17 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Efficacy of cytokine‑induced killer cells targeting CD40 and GITR

  • Authors:
    • Kaja D. Biederbick
    • Ingo G.H. Schmidt‑Wolf
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine III, University Hospital Bonn, D‑53105 Bonn, Germany, Department of Integrated Oncology, CIO Bonn, University Hospital Bonn, D‑53105 Bonn, Germany
  • Pages: 2425-2430
    |
    Published online on: December 18, 2018
       https://doi.org/10.3892/ol.2018.9849
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Since the publication of a novel protocol in 1991, cytokine‑induced killer (CIK) cells have shown promising results in the treatment against neoplastic diseases. Despite ongoing preclinical and clinical studies, CIK cell treatment in the context of human monoclonal antibodies targeting tumor‑necrosis factor receptors remains overlooked. The present study investigated whether a combination of CIK cells with human monoclonal antibody anti‑CD40 and anti‑Glucocorticoid‑induced TNF‑related protein (GITR) would lead to further cytotoxicity against tumor cells expressing CD40 and GITR ligand (L). Therefore, in vitro experiments with human lymphoma cell lines SU‑DHL‑4 and Daudi (both CD40 positive) and human breast adenocarcinoma MCF‑7 (GITRL positive) were performed and the secretion of interferon (IFN)‑γ was measured. Three interesting results emerged: i) a combination of CIK cells and anti‑CD40 mAb is more effective than CIK cell treatment alone; ii) the use of anti‑GITR mAb and CIK cells significantly enhanced the cytotoxicity of CIK cells against MCF‑7 compared with single CIK cell treatment and iii) the combination of both antibodies and CIK cells abrogates the anti tumoral effect of CIK cells on all three cell lines. By performing an ELISA for IFN‑γ measurement, a lower secretion was observed when anti‑CD40 or anti‑GITR mAb was added. This outcome indicates that further studies in vitro and in vivo may aid in understanding the synergistic molecular mechanisms of CIK cells, and anti‑CD40 and anti‑GITR mAb.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Bishop GA: The multifaceted roles of TRAFs in the regulation of B-cell function. Nat Rev Immunol. 4:775–786. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Pellat-Deceunynck C, Bataille R, Robillard N, Harousseau JL, Rapp MJ, Juge-Morineau N, Wijdenes J and Amiot M: Expression of CD28 and CD40 in human myeloma cells: A comparative study with normal plasma cells. Blood. 84:2597–2603. 1994.PubMed/NCBI

3 

Westendorf JJ, Ahmann GJ, Armitage RJ, Spriggs MK, Lust JA, Greipp PR, Katzmann JA and Jelinek DF: CD40 expression in malignant plasma cells. Role in stimulation of autocrine IL-6 secretion by a human myeloma cell line. J Immunol. 152:117–128. 1994.PubMed/NCBI

4 

Uckun FM, Gajl-Peczalska K, Myers DE, Jaszcz W, Haissig S and Ledbetter JA: Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. Blood. 76:2449–2456. 1990.PubMed/NCBI

5 

O'Grady JT, Stewart S, Lowrey J, Howie SE and Krajewski AS: CD40 expression in Hodgkin's disease. Am J Pathol. 144:21–26. 1994.PubMed/NCBI

6 

van Kooten C and Banchereau J: CD40-CD40 ligand. J Leukoc Biol. 67:2–17. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Banchereau J, Bazan F, Blanchard D, Brière F, Galizzi JP, van Kooten C, Liu YJ, Rousset F and Saeland S: The CD40 antigen and its ligand. Annu Rev Immunol. 12:881–922. 1994. View Article : Google Scholar : PubMed/NCBI

8 

Law CL, Gordon KA, Collier J, Klussman K, McEarchern JA, Cerveny CG, Mixan BJ, Lee WP, Lin Z, Valdez P, et al: Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40. Cancer Res. 65:8331–8338. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Costello RT, Gastaut JA and Olive D: What is the real role of CD40 in cancer immunotherapy? Immunol Today. 20:488–493. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Baltz KM, Krusch M, Bringmann A, Brossart P, Mayer F, Kloss M, Baessler T, Kumbier I, Peterfi A, Kupka S, et al: Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions. FASEB J. 21:2442–2454. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Baessler T, Krusch M, Schmiedel BJ, Kloss M, Baltz KM, Wacker A, Schmetzer HM and Salih HR: Glucocorticoid-induced tumor necrosis factor receptor-related protein ligand subverts immunosurveillance of acute myeloid leukemia in humans. Cancer Res. 69:1037–1045. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Buechele C, Baessler T, Wirths S, Schmohl JU, Schmiedel BJ and Salih HR: Glucocorticoid-induced TNFR-related protein (GITR) ligand modulates cytokine release and NK cell reactivity in chronic lymphocytic leukemia (CLL). Leukemia. 26:991–1000. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Schmidt-Wolf IG, Lefterova P, Mehta BA, Fernandez LP, Huhn D, Blume KG, Weissman IL and Negrin RS: Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells. Exp Hematol. 21:1673–1679. 1993.PubMed/NCBI

14 

Nwangwu CA, Weiher H and Schmidt-Wolf IGH: Increase of CIK cell efficacy by upregulating cell surface MICA and inhibition of NKG2D ligand shedding in multiple myeloma. Hematol Oncol. 35:2016.PubMed/NCBI

15 

He JY, Jia ZX, Cai XH, Han WM, Xiao R, Ma LD, Lu XZ, Zhou M and Chen BA: Roles of NKG2D in cytokine-induced killer (CIK) against hematological malignant cells lines. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 21:1380–1384. 2013.(In Chinese). PubMed/NCBI

16 

Verneris MR, Karimi M, Baker J, Jayaswal A and Negrin RS: Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. Blood. 103:3065–3072. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Zhao H, Fan Y, Li H, Yu J, Liu L, Cao S, Ren B, Yan F and Ren X: Immunotherapy with cytokine-induced killer cells as an adjuvant treatment for advanced gastric carcinoma: A retrospective study of 165 patients. Cancer Biother Radiopharm. 28:303–309. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Hao MZ, Lin HL, Chen Q, Ye YB, Chen QZ and Chen MS: Efficacy of transcatheter arterial chemoembolization combined with cytokine-induced killer cell therapy on hepatocellular carcinoma: A comparative study. Chin J Cancer. 29:172–177. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Yang B, Lu XC, Yu RL, Chi XH, Liu Y, Wang Y, Dai HR, Zhu HL, Cai LL and Han WD: Repeated transfusions of autologous cytokine-induced killer cells for treatment of haematological malignancies in elderly patients: A pilot clinical trial. Hematol Oncol. 30:115–122. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Schmeel LC, Schmeel FC, Coch C and Schmidt-Wolf IG: Cytokine-induced killer (CIK) cells in cancer immunotherapy: Report of the international registry on CIK cells (IRCC). J Cancer Res Clin Oncol. 141:839–849. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Wang Y, Xu Z, Zhou F, Sun Y, Chen J, Li L, Jin H and Qian Q: The combination of dendritic cells-cytotoxic T lymphocytes/cytokine-induced killer (DC-CTL/CIK) therapy exerts immune and clinical responses in patients with malignant tumors. Exp Hematol Oncol. 4:322015. View Article : Google Scholar : PubMed/NCBI

22 

Wang Z, Liu Y, Li R, Shang Y, Zhang Y, Zhao L, Li W, Yang Y, Zhang X, Yang T, et al: Autologous cytokine-induced killer cell transfusion increases overall survival in advanced pancreatic cancer. J Hematol Oncol. 9:62016. View Article : Google Scholar : PubMed/NCBI

23 

Jäkel CE and Schmidt-Wolf IG: An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells. Expert Opin Biol Ther. 14:905–916. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Jäkel CE, Vogt A, Gonzalez-Carmona MA and Schmidt-Wolf IG: Clinical studies applying cytokine-induced killer cells for the treatment of gastrointestinal tumors. J Immunol Res. 2014:8972142014. View Article : Google Scholar : PubMed/NCBI

25 

Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG and Weissman IL: Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med. 174:139–149. 1991. View Article : Google Scholar : PubMed/NCBI

26 

Cappuzzello E, Tosi A, Zanovello P, Sommaggio R and Rosato A: Retargeting cytokine-induced killer cell activity by CD16 engagement with clinical-grade antibodies. Oncoimmunology. 5:e11993112016. View Article : Google Scholar : PubMed/NCBI

27 

Hassan SB, Sørensen JF, Olsen BN and Pedersen AE: Anti-CD40-mediated cancer immunotherapy: An update of recent and ongoing clinical trials. Immunopharmacol Immunotoxicol. 36:96–104. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Szocinski JL, Khaled AR, Hixon J, Halverson D, Funakoshi S, Fanslow WC, Boyd A, Taub DD, Durum SK, Siegall CB, et al: Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: Induction of bax. Blood. 100:217–223. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Brady HJM and Gil-Gómez G: Molecules in focus Bax. The pro-apoptotic Bcl-2 family member, Bax. Int J Bio Cell Biol. 30:647–650. 1998. View Article : Google Scholar

30 

Martin S, Pahari S, Sudan R and Saha B: CD40 signaling in CD8+CD40+ T cells turns on contra-T regulatory cell functions. J Immunol. 184:5510–5518. 2010. View Article : Google Scholar : PubMed/NCBI

31 

McWhirter SM, Pullen SS, Holton JM, Crute JJ, Kehry MR and Alber T: Crystallographic analysis of CD40 recognition and signaling by human TRAF2. Proc Natl Acad Sci USA. 96:8408–8413. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T and Inoue J: Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40. Proc Natl Acad Sci USA. 96:1234–1239. 1999. View Article : Google Scholar : PubMed/NCBI

33 

Esparza EM and Arch RH: Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation. J Immunol. 174:7875–7882. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Melero I, Grimaldi AM, Perez-Gracia JL and Ascierto PA: Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clin Cancer Res. 19:997–1008. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Zhu BQ, Ju SW and Shu YQ: CD137 enhances cytotoxicity of CD3(+)CD56(+) cells and their capacities to induce CD4(+) Th1 responses. Biomed Pharmacother. 63:509–516. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Esser L, Weiher H and Schmidt-Wolf I: Increased efficacy of brentuximab vedotin (SGN-35) in combination with cytokine-induced killer cells in lymphoma. Int J Mol Sci. 17(pii): E10562016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Biederbick KD and Schmidt‑Wolf IG: Efficacy of cytokine‑induced killer cells targeting CD40 and GITR. Oncol Lett 17: 2425-2430, 2019.
APA
Biederbick, K.D., & Schmidt‑Wolf, I.G. (2019). Efficacy of cytokine‑induced killer cells targeting CD40 and GITR. Oncology Letters, 17, 2425-2430. https://doi.org/10.3892/ol.2018.9849
MLA
Biederbick, K. D., Schmidt‑Wolf, I. G."Efficacy of cytokine‑induced killer cells targeting CD40 and GITR". Oncology Letters 17.2 (2019): 2425-2430.
Chicago
Biederbick, K. D., Schmidt‑Wolf, I. G."Efficacy of cytokine‑induced killer cells targeting CD40 and GITR". Oncology Letters 17, no. 2 (2019): 2425-2430. https://doi.org/10.3892/ol.2018.9849
Copy and paste a formatted citation
x
Spandidos Publications style
Biederbick KD and Schmidt‑Wolf IG: Efficacy of cytokine‑induced killer cells targeting CD40 and GITR. Oncol Lett 17: 2425-2430, 2019.
APA
Biederbick, K.D., & Schmidt‑Wolf, I.G. (2019). Efficacy of cytokine‑induced killer cells targeting CD40 and GITR. Oncology Letters, 17, 2425-2430. https://doi.org/10.3892/ol.2018.9849
MLA
Biederbick, K. D., Schmidt‑Wolf, I. G."Efficacy of cytokine‑induced killer cells targeting CD40 and GITR". Oncology Letters 17.2 (2019): 2425-2430.
Chicago
Biederbick, K. D., Schmidt‑Wolf, I. G."Efficacy of cytokine‑induced killer cells targeting CD40 and GITR". Oncology Letters 17, no. 2 (2019): 2425-2430. https://doi.org/10.3892/ol.2018.9849
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team