Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Immune response and survival of refractory cancer patients who received TGF-β2 antisense/GM-CSF gene modified autologous tumor cell (TAG) vaccine

Gene Therapy volume 20, pages 875–879 (2013)Cite this article

Subjects

Abstract

TAG vaccine is a novel ‘triad vaccine’ that involves transfection of autologous tumor with a dual plasmid, TGFβ2 antisense gene and GM-CSF gene. Patients with advanced cancer who failed standard therapy were treated. IFN-γ ELISPOT analysis (Enzyme-Linked Immunospot Assay for Interferon Gamma) using TAG autologous vaccine target cells was performed prior to vaccination and at week 12 after the third vaccination. The purpose of this assessment was to correlate the IFN-γ ELISPOT immune response with long-term survival of advanced cancer patients who received TAG vaccination. Twenty-three of 28 patients received ⩾3 TAG vaccinations (two patients withdrew consent and three had disease progression prior to the third vaccination). Eleven patients demonstrated a positive ELISPOT response (>10 spots and ⩾2 × baseline) at week 12 and 12 patients did not (P=0.002). Median survival from time of treatment between ELISPOT-positive and -negative groups was significantly different (550 vs 159 days, P=0.036), as was median survival from the time of procurement (627 vs 257 days, respectively, P=0.043). In conclusion, the IFN-γ ELISPOT assay may provide an effective measure of immune response following treatment with ‘triad vaccines’, but additional patient numbers and/or other immune modulatory parameters are necessary for future testing.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

References

  1. Nemunaitis J, Sterman D, Jablons D, Smith JW, Fox B, Maples P et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004; 96: 326–331.

    Article  CAS  Google Scholar 

  2. Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol 2006; 24: 4721–4730.

    Article  CAS  Google Scholar 

  3. Olivares J, Kumar P, Yu Y, Maples PB, Senzer N, Bedell C et al. Phase I trial of TGF-{beta}2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin Cancer Res 2011; 17: 183–192.

    Article  CAS  Google Scholar 

  4. Nemunaitis JJ . Are vaccines making a comeback in non-small-cell lung cancer? J Clin Oncol 2008; 26: 1402–1403.

    Article  Google Scholar 

  5. Wheler J, Tsimberidou AM, Hong D, Naing A, Jackson T, Liu S et al. Survival of patients in a Phase 1 Clinic: the M D Anderson Cancer Center experience. Cancer 2009; 115: 1091–1099.

    Article  Google Scholar 

  6. Corbiere V, Chapiro J, Stroobant V, Ma W, Lurquin C, Lethe B et al. Antigen spreading contributes to MAGE vaccination-induced regression of melanoma metastases. Cancer Res 2011; 71: 1253–1262.

    Article  CAS  Google Scholar 

  7. Chiang CL, Benencia F, Coukos G . Whole tumor antigen vaccines. Sem Immunol 2010; 22: 132–143.

    Article  CAS  Google Scholar 

  8. Moodie Z, Price L, Gouttefangeas C, Mander A, Janetzki S, Lower M et al. Response definition criteria for ELISPOT assays revisited. Cancer Immunol Immunother 2010; 59: 1489–1501.

    Article  CAS  Google Scholar 

  9. Samri A, Durier C, Urrutia A, Sanchez I, Gahery-Segard H, Imbart S et al. Evaluation of the interlaboratory concordance in quantification of human immunodeficiency virus-specific T cells with a gamma interferon enzyme-linked immunospot assay. Clin Vaccine ImmunolI 2006; 13: 684–697.

    Article  CAS  Google Scholar 

  10. Comin-Anduix B, Gualberto A, Glaspy JA, Seja E, Ontiveros M, Reardon DL et al. Definition of an immunologic response using the major histocompatibility complex tetramer and enzyme-linked immunospot assays. Clin Cancer Res 2006; 12: 107–116.

    Article  CAS  Google Scholar 

  11. Maples PB, Kumar P, Yu Y, Wang Z, Jay CM, Pappen BO et al. FANG vaccine: autologous tumor vaccine genetically modified to express GM-CSF and block production of furin. Bioprocess J 2010; 8: 4–14.

    Article  Google Scholar 

  12. Kumar P, Jay C, Oxendine I, Nemunaitis J, Maples PB . TAG Xenograft Vaccine: Xenograft-Expanded Autologous Tumor Vaccine Genetically Modified to Express GM-CSF and Block TGFβ2. Bioprocess J 2009; 8: 30–36.

    Article  CAS  Google Scholar 

  13. Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M et al. Phase I Trial of ‘bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell’ vaccine (FANG) in advanced cancer. Mol Ther 2012; 20: 679–686.

    Article  CAS  Google Scholar 

  14. Nemunaitis J . Multifunctional vaccines in cancer: the 'triad' approach. Expert Rev Vaccines 2011; 10: 713–715.

    Article  Google Scholar 

  15. Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad ScUSA 2008; 105: 3005–3010.

    Article  CAS  Google Scholar 

  16. Iwata M, Ohoka Y, Kuwata T, Asada A . Regulation of T cell apoptosis via T cell receptors and steroid receptors. Stem Cells 1996; 14: 632–641.

    Article  CAS  Google Scholar 

  17. Zachariae CO . Chemotactic cytokines and inflammation. Biological properties of the lymphocyte and monocyte chemotactic factors ELCF, MCAF and IL-8. Acta Derm Venereol Suppl 1993; 181: 1–37.

    CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the generous support of the Jasper L and Jack Denton Wilson Foundation, the Summerfield G Roberts Foundation, the Crowley–Carter Foundation, the Crowley Shanahan Foundation, the Linda Tallen and David Paul Kane Cancer Educational and Research Foundation, the Marilyn Augur Family Foundation and Gradalis, Inc. We would also like to thank Susan W Mill for her competent and knowledgeable assistance in the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Clinical Research, Mary Crowley Cancer Research Centers, Dallas, TX, USA

    J Nemunaitis & N Senzer

  2. Gradalis, Inc., Dallas, TX, USA

    J Nemunaitis, N Senzer, P Kumar, T Nemunaitis, Y Yu, G Wallraven, B O Pappen & P B Maples

  3. Texas Oncology, PA, Dallas, TX, USA

    J Nemunaitis, N Senzer, J Olivares & M Barve

  4. Medical City Dallas Hospital, Dallas, TX, USA

    J Nemunaitis & N Senzer

  5. WLS Surgical Associates, PA, Dallas, TX, USA

    J Kuhn

  6. Cardiovascular Specialty Associates of North Texas, PA, Dallas, TX, USA

    M Magee

Authors
  1. J Nemunaitis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Senzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Olivares
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Barve
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Nemunaitis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Magee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Wallraven
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B O Pappen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P B Maples
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Nemunaitis.

Ethics declarations

Competing interests

The following authors are shareholders in Gradalis Inc.: John Nemunaitis, Neil Senzer and Phillip Maples. All other authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nemunaitis, J., Senzer, N., Olivares, J. et al. Immune response and survival of refractory cancer patients who received TGF-β2 antisense/GM-CSF gene modified autologous tumor cell (TAG) vaccine. Gene Ther 20, 875–879 (2013). https://doi.org/10.1038/gt.2013.9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gt.2013.9

Keywords

  • cancer
  • immune response
  • vaccine
  • clinical
  • GM-CSF

Search

Advanced search

Quick links