Journal of Neuro-Oncology

, Volume 48, Issue 2, pp 113–120

A Pilot Study of Autologous Cancer Cell Vaccination and Cellular Immunotherapy Using Anti-CD3 Stimulated Lymphocytes in Patients with Recurrent Grade III/IV Astrocytoma

  • Gary W. Wood
  • Frank P. Holladay
  • Teresa Turner
  • Yu-Ying Wang
  • Masahiro Chiga
Article

Abstract

The study objectives were to determine; (1) whether activated T cells could be generated from peripheral blood of patients immunized with their own cancer cells, (2) whether adoptive transfer of the activated T cells to patients had toxic effects and (3) whether the infused cells produced clinical responses. Study patients had recurrent, surgically accessible grade III/IV astrocytomas. The patients were tapered off steroids after total surgical resection and immunized with autologous cancer cells plus Bacillus, Calmette and Guerin (BCG). Peripheral blood mononuclear cells were activated with anti-CD3, expanded with interleukin-2 (IL-2) and reinfused to patients. The number of activated T cells that was given back to patients varied between 1010 and 1011. Side effects that were observed following immunization and adoptive cell transfer included mainly transient flu-like symptoms. One patient's tumor partially regressed, but there was no effect on survival. Two other patients' tumors regressed, and the patients are apparently disease-free more than 5 and 4 years later. The other six patients' tumors were apparently unaffected by the treatment. Patient age, tumor grade and CD4/CD8 composition of infused cells were positively correlated with clinical responses. Cellular immunotherapy is feasible and is associated with minimal toxicity. Additional appropriately controlled studies will be required to determine whether cellular immunotherapy could be used as a treatment for central nervous system malignancy. Additional studies also will be required to determine the underlying immunological mechanisms.

anti-CD3 astrocytoma glioma immunotherapy T cell tumor immunology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Chang AE, Shu S: Current status of immunotherapy of cancer. Crit Rev Oncol-Hematol 22: 213-228, 1996Google Scholar
  2. 2.
    Shu S, Plautz GE, Krauss JC, Chang AE: Tumor immunology. JAMA 278: 1972-1981, 1997Google Scholar
  3. 3.
    Chang AE, Aruga A, Cameron MJ, Sondak VK, Normolle, DP, Fox BA, Shu S: Adoptive immunotherapy with vaccine primed lymph node cells secondarily activated with anti-CD3 and interleukin 2. J Clin Oncol 15: 796-807, 1997Google Scholar
  4. 4.
    Holladay FP, Heitz T, Chen Y-L, Wood GW: Successful treatment of a malignant rat glioma with cytotoxic T cells. Neurosurgery 31: 528-533, 1992Google Scholar
  5. 5.
    Holladay FP, Heitz T and Wood, GW: Cytotoxic T lymphocytes, but not lymphokine activated killer cells, exhibit antitumor activity against established intracerebral gliomas. J Neurosurg 77: 757-762, 1992Google Scholar
  6. 6.
    Holladay FP, Lopez G, De M, Morantz RA, Wood GW: Generation of cytotoxic immune responses against a rat glioma by in vivo priming and secondary in vitro stimulation with tumor cells. Neurosurgery 30: 499-505, 1992Google Scholar
  7. 7.
    Holladay FP, Wood GW: Generation of cellular immune responses against a glioma-associated antigen(s). J Neuroimmunol 44: 27-32, 1993Google Scholar
  8. 8.
    Plautz GE, Toualisky JE, Shu S: Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor draining lymph node cells. Cell Immunol 178: 101-107, 1997Google Scholar
  9. 9.
    Rice CD, Baldwin NG, Biron RT, Bear HD, Merchant RE: Ex vivo expansion of tumor-draining lymph node cells using compounds which activate intracellular signal transduction. II. Cytokine production and in vivo efficacy of gliomasensitized lymphocytes. J Neuro-Oncol 32: 29-38, 1997Google Scholar
  10. 10.
    Wood GW, Turner T, Wang Y-Y, Holladay FP: Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats. J Immunotherapy 22: 497-505, 1999Google Scholar
  11. 11.
    Berger MS, Tucker A, Spence A, Winn HR: Reoperation for glioma. Clin Neurosurgery 39: 172-186, 1992Google Scholar
  12. 12.
    Dirks P, Bernstein M, Muller PJ, Tucker WS: The value of reoperation for recurrent glioblastoma. Can J Surg 36: 271-275, 1993Google Scholar
  13. 13.
    Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J 2nd, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. New Engl J Med 303: 1323-1329, 1980Google Scholar
  14. 14.
    Fumari FB, Huang HJ, Cavenee WK: Genetics and malignant progression of human brain tumours Cancer Surv 25: 233-275, 1995Google Scholar
  15. 15.
    van der Bruggen P, van den Eynde B: Molecular definition of cancer antigens recognized by T lymphocytes. Curr Opin Immunol 4: 608-666, 1992Google Scholar
  16. 16.
    Srivastava PK: Do human tumors contain shared protective antigens? Or the necessity of remembrance of things past. Semin Immunol 8: 295-302, 1996Google Scholar
  17. 17.
    Holladay FP, Heitz-Turner T, Bayer WL, Wood GW: Autologous tumor cell vaccination combined with adoptive cellular immunotherapy in patients with grade III/IV astrocytoma. J Neuro-Oncol 27: 179-189, 1996Google Scholar
  18. 18.
    Chang AE, Yoshizawa H, Sakai K, Cameron MJ, Sondak V, Shu S: Clinical observations on adoptive immunotherapy with vaccine-primed T lymphocytes secondarily sensitized with tumor in vitro. Cancer Res 53: 1043-1050, 1993Google Scholar
  19. 19.
    Yoshizawa H, Chang AE, Shu S: Specific adoptive immunotherapy mediated by tumor-draining lymph node cells sequentially activated with anti-CD3 and IL-2. J Immunol 147: 729-737, 1991Google Scholar
  20. 20.
    Plautz GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC, Shu, S: Systemic adoptive immunotherapy of malignant gliomas. J Neurosurg 89: 42-51, 1998Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Gary W. Wood
    • 1
  • Frank P. Holladay
    • 2
  • Teresa Turner
    • 1
  • Yu-Ying Wang
    • 1
  • Masahiro Chiga
    • 1
  1. 1.Department of PathologyUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Providence Medical CenterKansas CityUSA

Personalised recommendations