Journal of Neuro-Oncology

, Volume 4, Issue 4, pp 329–336 | Cite as

Establishment of interleukin 2 dependent cytotoxic T lymphocyte cell line specific for autologous brain tumor and its intracranial administration for therapy of the tumor

  • Toshiki Kitahara
  • Osamu Watanabe
  • Akira Yamaura
  • Hiroyasu Makino
  • Takashi Watanabe
  • Gen Suzuki
  • Ko Okumura


Autologous brain tumor specific CTLs were induced from the patient's PBL by a mixed lymphocyte-tumor culture, and were maintained for more than 2 months in a medium containing exogenous ILr2. The autologous T cell line containing specific CTL was administered into the tumor-bed for the treatment of malignant glioma. In 2 cases out of 5, tumors regressed more than 50% in diameter. One of these patients is still alive now with full of his social activities, and it is 104 weeks after the initiation of the immunotherapy. Autologous T cell lines were safely administered in all cases without any complications nor toxicities.


adoptive immunotherapy cytotoxic T lymphocyte interleukin 2 brain tumor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Millis GB, Carlson G, Paetkau V: Generation of cytotoxic lymphocytes to syngeneic tumors by using co-stimulator (interleukin 2); in vivo activity. J Immunol 125:1904–1909, 1980.Google Scholar
  2. 2.
    Cheever MA, Greenberg PD, Fefer A: Specific adoptive therapy of established leukemia with syngeneic lymphocytes sequentially immunized in vivo and in vitro and non-specifically expanded by culture with interleukin 2. J Immunol 126:1318–1322, 1981.Google Scholar
  3. 3.
    Cheever MA, Greenberg PD, Fefer A, Gillis S: Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med 155:968–980, 1982.Google Scholar
  4. 4.
    Eberlein TJ, Rosenstein M, Spiess P, Wesley R, Rosenberg SA: Adoptive chemoimmunotherapy of a syngeneic murine lymphoma with long-term lymphoid cell lines expanded in T cell growth factor. Cancer Immunol Immunother 13:5–13, 1982.Google Scholar
  5. 5.
    Eberlein TJ, Rosenstein M, Rosenberg SA: Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med 156:385–397, 1982.Google Scholar
  6. 6.
    Adler A, Stein JA, Kedar E, Naor D, Weiss DW: Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: A pilot study. J Biol Resp Modif 3:491–500, 1984.Google Scholar
  7. 7.
    Rosenberg SA: Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Resp Modif 3:501–511, 1984.Google Scholar
  8. 8.
    Mazumder A, Eberlein TJ, Grim EA, Wilsod D, Keenan AM, Aamodt R, Rosenberg SA: Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer 53:896–905, 1984.Google Scholar
  9. 9.
    Slankard-Chahinian M, Holland JF, Gordon RE, Becker J, Ohnuma T. Adoptive autoimmunotherapy: Cytotoxic effect of an autologous long-term T cell line on malignant melanoma. Cancer 53:1066–1072, 1984.Google Scholar
  10. 10.
    Kohler PC, Hank JA, Exten R, Minkoff DZ, Wilson DG, Sondel PM: Clinical response of a patient with diffuse histiocytic lymphoma to adoptive chemoimmunotherapy using cyclophosphamide and alloactivated haploidentical lymphocytes: A case report and phase I trial. Cancer 55:552–560, 1985Google Scholar
  11. 11.
    Rosenberg SA, Lotze MT, Muul LM, Leitmann 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 lymphokineactivated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1489, 1985.PubMedGoogle Scholar
  12. 12.
    Coakham HB, Lashmi MS: Tumor-associated surface antigen(s) in human astrocytomas. Oncology 31:233–243, 1975.Google Scholar
  13. 13.
    Wikstrand CJ, Mahaley MS, Bigner DD: Surface antigenic characteristics of human glial brain tumor. Cancer Rec 37:4267–4275, 1977.Google Scholar
  14. 14.
    Keheyov IR: Tumor-associated water soluble antigen(s) in human glioblastoma demonstrated by immunodiffusion and immunoelectrophoresis. Ann Immunol 127c:703–716, 1976.Google Scholar
  15. 15.
    Pfreundschuh M, Shiku H, Takahashi T: Serological analysis of cell surface antigens of malignant human brain tumors. Proc Natl Acad Sci USA 75:5122–5126, 1978.Google Scholar
  16. 16.
    Levy NL: Specificity of lymphocyte-mediated cytotoxicity in patients with primary intracranial tumors. J Immunol 121:903–915, 1978.Google Scholar
  17. 17.
    Rainbird S, Allwood G, Ridley A: Lymphocyte-mediated cytotoxicity against gliomas. Brain 104:451–464, 1981.Google Scholar
  18. 18.
    Young HF, Kaplan A: Immunotherapy of human gliomas. In: Waters H (ed) Immunotherapy. The handbook of cancer immunology. Garland STPM Press, New York, 1978, Vol 5, pp 375–382.Google Scholar
  19. 19.
    Young HF, Kaplan A, Regelson W: Immunotherapy with autologous white cell infusions (‘lymphocytes’) in the treatment of recurrent glioblastoma multiforme. A preliminary report. Cancer 40:1037–1044, 1977.Google Scholar
  20. 20.
    Scher I, Maje MG: Cellular identification and separation. In: Paul WE (ed) Fundamental immunology. Raven Press, New York, 1984, pp 767–780.Google Scholar
  21. 21.
    Hünig TR, Bevan MJ: Antigen recognition by cloned cytotoxic T lymphocytes followed rules predicted by the alteredself hypothesis. J Exp Med 155:111–117, 1982.Google Scholar
  22. 22.
    Karnofsky DA, Ableman WH, Craver LF, Burchenal JH: The use of the nitrogen mustards in the palliative treatment of carcinoma with particular reference to bronchogenic carcinoma. Cancer 1:634–656, 1948.Google Scholar

Copyright information

© Martinus Nijhoff Publishers 1987

Authors and Affiliations

  • Toshiki Kitahara
    • 1
  • Osamu Watanabe
    • 2
  • Akira Yamaura
    • 1
  • Hiroyasu Makino
    • 1
  • Takashi Watanabe
    • 3
  • Gen Suzuki
    • 4
  • Ko Okumura
    • 5
  1. 1.Department of Neurological SurgeryChiba University School of MedicineChibashi, ChibaJapan
  2. 2.Department of NeurosurgeryChiba Rosai HospitalJapan
  3. 3.Department of NeurosurgeryTokyo Metropolitan Ebara General HospitalJapan
  4. 4.Division of Radiation HealthNational Institute of Radiological SciencesJapan
  5. 5.Department of ImmunologyJuntendo University School of MedicineJapan

Personalised recommendations