Log in

Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

We have cultured peripheral blood lymphocytes (PBL) from glioblastoma patients in recombinant interleukin-2 (IL-2) containing medium for a period of 5 days. The cytotoxicity of these cells was tested on 51Cr-labelled autologous dissociated glioblastoma cells which had not been cultured. Significant cytotoxicity against glioma cells was observed in seven out of nine cases. IL-2 activated PBL from normal donors were equally cytotoxic against these glioma cells. Autologous lymphocytes activated by phytohaemagglutinin were also lysed in most cases, and the erythroleukemia cell line K562 was highly susceptible to the cytotoxic capability of the IL-2 activated PBL. In cold target inhibition experiments, K562 inhibited the cytotoxicity against both autologous and allogenic glioma cells, and glioma cells inhibited the cytotoxicity against K562. Following immunomagnetic separation, the IL2 activated cells demonstrated cytotoxicity against glioma cells, K562 cells, and PHA blasts in both the CD8+ and the CD8 subsets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. New Engl J Med 313:1485–1492, 1985

    Google Scholar 

  2. Rosenberg SA, Lotze MT. Cancer immunotherapy using interleukin-2 and interleukin-2 activated lymphocytes. Annu Rev Immunol 4:681–709, 1986

    Google Scholar 

  3. Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA: In vitro killing of human glioblastoma by interleukin-2 activated autologous lymphocytes. J Neurosurg 64:114–117, 1986

    Google Scholar 

  4. Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA: Ianterleukin-2 and autologous lymphokine-activated killer cells in the treatment of malignant glioma. J Neurosurg 64:743–749, 1986

    Google Scholar 

  5. Miyatake S, Handa H, Yamashita J, Yamasaki T, Ueda M, Namba Y, Hanaoka M: Induction of human glioma-specific cytotoxic T -lymphocyte lines by autologous tumor stimulation and interleukin-2. J Neuro-Oncol 4:55–64, 1986

    Google Scholar 

  6. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA: Lymphokine-activated killer cell phenomenon: lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841, 1982

    Google Scholar 

  7. Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA: Lymphokine-activated killer cell phenomenon II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 157:884–897, 1983

    Google Scholar 

  8. Phillips JH, Lanier LL: Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 164:814–825, 1986

    Google Scholar 

  9. Ortaldo JR, Mason A, Overton R: Lymphokine activated killer cells. Analysis of progenitors and effectors. J Exp Med 164:1193–1205, 1986

    Google Scholar 

  10. Hirschberg H, Skare H, Thorsby E: Cell mediated lympholysis: CML. A microplate technique requiring few target cells and employing a new method of supernatant collection. J Immunol Meth 16:131–141, 1977

    Google Scholar 

  11. Gaudernack G, Leivestad T, Ugelstad J, Thorsby E: Isolation of pure functionally active CD8+ T cells. Positive selection with monoclonal antibodies directly conjugated to monosized magnetic microspheres. J Immunol Meth 90:179–187, 1986

    Google Scholar 

  12. Leivestad T, Gaudernack G, Ugelstad J, Thorsby E: Positive selection of activated T cells of the T8 (CD8) sub-type by immunomagnetic separation. Tissue Antigens 28:46–52, 1986

    Google Scholar 

  13. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA: Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 41:4420–4425, 1981

    Google Scholar 

  14. Grimm EA, Wilson DJ: The human lymphokine activated killer cell system V. Purified recombinant interleukin 2 activates cytotoxic lymphocytes which lyse both natural killer-resistant autologous and allogeneic tumors and trinitrophenyl-modified autologous peripheral blood lymphocytes. Cell Immunol 94:568–578, 1985

    Google Scholar 

  15. Muul LM, Director EP, Hyatt CL, Rosenberg SA: Large scale production of human lymphokine activated killer cells for use in adoptive immunotherapy. J Immunol Meth 88:265–275, 1986

    Google Scholar 

  16. Sondel PM, Hank JA, Kohler PC, Chen BP, Minkoff DZ, Molenda JA: Destruction of autologous human lymphocytes by interleukin 2-activated cytotoxic cells. J Immunol 137:502–511, 1986

    Google Scholar 

  17. Rayner AA, Grimm EA, Lotze MT, Wilson DJ, Rosenberg SA: Lymphokine-activated killer (LAK) cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumor cells from autologous and multiple allogeneic tumors. J Natl Cancer Inst 75:67–75, 1985

    Google Scholar 

  18. Allavena P, Ortaldo JR: Characteristics of human NK clones: Target specificity and phenotype. J Immunol 132:2363–2369, 1984

    Google Scholar 

  19. Hercend T, Reinherz EL, Meuer S, Schlossman SF, Ritz J: Phenotypic and functional heterogeneity of human cloned natural killer cell lines. Nature 301:158–160, 1983

    Google Scholar 

  20. Mazumder A, Rosenberg SA: Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J Exp Med 159:495–507, 1984

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bosnes, V., Hirschberg, H. Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro . J Neuro-Oncol 6, 85–92 (1988). https://doi.org/10.1007/BF00163545

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00163545

Key words

Navigation