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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
January-2015 Volume 46 Issue 1

Full Size Image

Cover Legend PDF

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
January-2015 Volume 46 Issue 1

Full Size Image

Cover Legend PDF

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

Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study

  • Authors:
    • Volker Schirrmacher
    • Christoph Schlude
    • Jürgen Weitz
    • Philipp Beckhove
  • View Affiliations / Copyright

    Affiliations: German Cancer Research Center, Division of Translational Immunology; Department of Surgical Oncology, Heidelberg University Hospital, Heidelberg, Germany
  • Pages: 71-77
    |
    Published online on: October 6, 2014
       https://doi.org/10.3892/ijo.2014.2692
  • 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

T‑cell costimulation is necessary to induce a response of naïve T cells. Whether T‑cell costimulation can also cause reactivation of unreactive, possibly anergized memory T cells (MTCs) from late‑stage cancer patients is unknown. To investigate this question, we developed a bispecific anti‑CD28 fusion protein (bsHN‑CD28) which can easily be attached to the vaccine ATV‑NDV. This virus‑modified autologous tumor cell vaccine has already shown effectivity in colon cancer patients following resection of liver metastases. In this phase Ⅰ clinical study, 14 colorectal carcinoma (CRC) patients with late‑stage disease which could not be operated anymore with curative intent were treated with the vaccine ATV‑NDV to which bsHN‑CD28 was attached. No severe adverse events were recorded. All patients showed an immunological response of tumor‑reactive T cells, at least once during the course of five vaccinations. Also, we demonstrate a dose‑response relationship with the costimulatory molecule added to the vaccine. A partial response of metastases was documented in four patients. The study suggests that the three‑component vaccine is safe and can reactivate possibly anergized T cells from a chronic disease like advanced‑stage cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Fong Y, Fortner J, Sun RL, Brennan MF and Blumgart LH: Clinical score for predicting recurrence after hepatic resection of metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 230:309–318. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Galon J, Costes A, Sanchez-Cabo F, et al: Type, density, and location of immune cells within colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Ockert D, Schirrmacher V, Beck N, et al: Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. Clin Cancer Res. 2:21–28. 1996.

4 

Schirrmacher V, Fournier P and Schlag P: Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: long-term patient survival and mechanism of function. Exp Rev Vaccines. 13:117–130. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Schulze T, Kemmner W, Weitz J, et al: Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial. Cancer Immunol Immunother. 58:61–69. 2009. View Article : Google Scholar

6 

Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Schwartz RH: T cell anergy. Annu Rev Immunol. 21:305–334. 2003. View Article : Google Scholar

8 

Greenfield EA, Nguyen KA and Kuchroo VK: CD28/B7 costimulation: a review. Crit Rev Immunol. 18:389–418. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Fournier P and Schirrmacher V: Bispecific antibodies and trispecific immunocytokines for targeting the immune system against cancer: preparing for the future. BioDrugs. 27:35–53. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Aigner M, Janke M, Lulei M, Beckhove P, Fournier P and Schirrmacher V: An effective tumor vaccine optimized for costimulation via bispecific and trispecific fusion proteins. Int J Oncol. 32:777–789. 2008.PubMed/NCBI

11 

Haas C, Lulei M, Fournier P, Arnold A and Schirrmacher V: T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine. Vaccine. 23:2439–2453. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Haas C, Lulei M, Fournier P, Arnold A and Schirrmacher V: A tumor vaccine containing anti-CD3 and anti-CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes. Int J Cancer. 118:658–667. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Koch M, Beckhove P, Op den Winkel J, et al: Tumor infiltrating T lymphocytes in colorectal cancer: Tumor-selective activation and cytotoxic activity in situ. Ann Surg. 244:986–992. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Sommerfeldt N, Schütz F, Sohn C, Förster J, Schirrmacher V and Beckhove P: The shaping of a polyvalent and highly individual T-cell repertoire in the bone-marrow of breast cancer patients. Cancer Res. 66:8258–8265. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Termeer CC, Schirrmacher V, Bröcker EB and Becker JC: Newcastle disease virus infection induces B7-1/B7-2-independent T-cell costimulatory activity in human melanoma cells. Cancer Gene Ther. 7:316–323. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Bai L, Koopmann J, Fiola C, Fournier P and Schirrmacher V: Dendritic cells pulsed with viral oncolysates potently stimulate autologous T cells from cancer patients. Int J Oncol. 21:685–694. 2002.PubMed/NCBI

17 

Brischwein K, Schlereth B, Guller B, et al: MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol. 43:1129–1143. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Biburger M, Weth R and Wels WS: A novel bispecific tetravalent antibody fusion protein to target costimulatory activity for T-cell activation to tumor cells overexpressing ErbB2/HER2. J Mol Biol. 346:1299–1311. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Müller D, Frey K and Kontermann RE: A novel antibody-4-1BBL fusion protein for targeted costimulation in cancer immunotherapy. J Immunother. 31:714–722. 2008.PubMed/NCBI

20 

Schirrmacher V, Haas C, Bonifer R, Ahlert T, Gerhards R and Ertel C: Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus. Gene Ther. 6:63–73. 1999. View Article : Google Scholar

21 

Fournier P, Wilden H and Schirrmacher V: Importance of retinoic acid-inducible gene I and of receptor for Type I interferon for cellular resistance to infection by Newcastle disease virus. Int J Oncol. 40:287–298. 2012.PubMed/NCBI

22 

Washburn B and Schirrmacher V: Human tumor cell infection by Newcastle Disease Virus leads to upregulation of HLA and cell adhesion molecules and to induction of interferons, chemokines and finally apoptosis. Int J Oncol. 21:85–93. 2002.

23 

Grakoui A, Bromley SK, Sumen C, et al: The immunological synapse: a molecular machine controlling T cell activation. Science. 285:221–227. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Zitvogel L, Tesniere A and Kroemer G: Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 6:715–727. 2006. View Article : Google Scholar : PubMed/NCBI

25 

St Clair EW: The calm after the cytokine storm: lessons from the TGN1412 trial. J Clin Invest. 118:1344–1347. 2008.PubMed/NCBI

26 

Feuerer M, Beckhove P, Bai L, Solomayer EF, Bastert G, Diehl IJ, Pedain C, Oberniedermayr M, Schirrmacher V and Umansky V: Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med. 7:452–458. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Feuerer M, Beckhove P, Garbi N, Mahnke Y, Limmer A, Hommel M, Hämmerling GJ, Kyewsky B, Hamann A, Umansly V and Schirrmacher V: Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nat Med. 9:1151–1157. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Schirrmacher V, Feuerer M, Fournier P, Ahlert T, Umansky V and Beckhove P: T-cell priming in bone marrow: the potential for long-lasting protective anti-tumor immunity. Trends Mol Med. 9:526–534. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Schirrmacher V, Schlude C, Weitz J and Beckhove P: Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study. Int J Oncol 46: 71-77, 2015.
APA
Schirrmacher, V., Schlude, C., Weitz, J., & Beckhove, P. (2015). Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study. International Journal of Oncology, 46, 71-77. https://doi.org/10.3892/ijo.2014.2692
MLA
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46.1 (2015): 71-77.
Chicago
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46, no. 1 (2015): 71-77. https://doi.org/10.3892/ijo.2014.2692
Copy and paste a formatted citation
x
Spandidos Publications style
Schirrmacher V, Schlude C, Weitz J and Beckhove P: Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study. Int J Oncol 46: 71-77, 2015.
APA
Schirrmacher, V., Schlude, C., Weitz, J., & Beckhove, P. (2015). Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study. International Journal of Oncology, 46, 71-77. https://doi.org/10.3892/ijo.2014.2692
MLA
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46.1 (2015): 71-77.
Chicago
Schirrmacher, V., Schlude, C., Weitz, J., Beckhove, P."Strong T‑cell costimulation can reactivate tumor antigen‑specific T cells in late‑stage metastasized colorectal carcinoma patients: Results from a phase Ⅰ clinical study". International Journal of Oncology 46, no. 1 (2015): 71-77. https://doi.org/10.3892/ijo.2014.2692
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