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Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) Lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA

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Abstract

Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumorin vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safein vivo and more effective than IL-2 triggering enhanced effector functionin vitro.

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References

  1. Chong ASF, Aleksijevic A, Scuderi P, Hersh EM, Grimes WJ: Phenotypic and functional analysis lymphokine-activated killer (LAK) cell clones. Cancer Immunol Immunother 29: 270–278, 1989

    Google Scholar 

  2. Grimm EA, Rosenberg SA: The human lymphokine-activated killer cell phenomenon. Lymphokines 9: 279–311, 1984

    Google Scholar 

  3. Kalland T, Belfrage H, Bhiladvala P, Hedlund G: Analysis of the murine lymphokine-activated killer (LAK) cell phenomenon: dissection of effectors and progenitors into NK- and T-like cells. J Immunol 138: 3640–3645, 1987

    Google Scholar 

  4. Yamamoto R, Coss J, Vayuvegula B, Gupta S, Beamer Y, Jacques S, Jeffes E, Carson W, Jakowatz J, Granger G: Generation of stimulated, lymphokine activated T killer (T-LAK) cells from the peripheral blood of normal donors and adult patients with recurrent glioblastoma. J Immunological Methods 137: 225–235, 1991

    Google Scholar 

  5. George RE, Loudon WG, Moser RP, Bruner JM, Steck PA, Grimm EA:In vitro cytolysis of primitive neuroectodermal tumors of the posterior fossa (medulloblastoma) by lymphokine-activated killer cells. J Neurosurg 69:403–409, 1988

    Google Scholar 

  6. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze ST, Yany JC, Seipp C, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE: Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. New Eng J Med 319: 1676–1680, 1988

    Google Scholar 

  7. Rosenberg SA, Spiess P, Lafreniere R: A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233: 1318–1321, 1986

    Google Scholar 

  8. Lafreniere R, Rosenberg SA: Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer cells and recombinant interleukin 2 can mediate the regression of both immunogeneic and nonimmunogenic sarcomas and an adenocarcinoma. J Immunol 135: 4273–4280, 1985

    Google Scholar 

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

    Google Scholar 

  10. Mule JJ, Shu S, Schwartz SL, Rosenberg SA: Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 225: 1487–1489, 1984

    Google Scholar 

  11. Mule JJ, Shu S, Rosenberg SA: The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2in vivo. J Immunol 135: 646–652, 1985

    Google Scholar 

  12. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316: 889–897, 1987

    Google Scholar 

  13. Takai N, Tanaka R, Yoshida S, Hara N, Takafumi S:In vivo andin vitro effect of adoptive immunotherapy of experimental murine brain tumors using lymphokine-activated killer cells. Cancer Res 48: 2047–2052, 1988

    Google Scholar 

  14. VanHaelst-Pisani CM, Pisani RJ, Kovach JS: Cancer immunotherapy: current status of treatment with interleukin 2 and lymphokine-activated killer cells. Mayo Clin Proc 64: 451–465, 1989

    Google Scholar 

  15. Kornblith PL, Walker MD, Cassady JR (eds): General principles of treatment, in Neurologic Oncology, Philadelphia, J.B. Lippincott Company, 1987, pp 93–113

    Google Scholar 

  16. Saloman M: Malignant glioma management. Neurosurg Clin N A 1: 49–63, 1990

    Google Scholar 

  17. Saloman M: Survival in Glioblastoma: Historical Perspective. Neurosurgery 7: 435–439, 1980

    Google Scholar 

  18. Carson W, Jakowatz J, Yamamoto R, Fitzgerald T, Gupta S, Vayuvegula B, Lucci J, Beckman M, Dulkanchainun S, Granger G, Jeffes E: Rat mitogen-stimulated lymphokine-activated (MAK) T killer cells: Production and effects on C6 Glioma Cellin vitro andin vivo in the brain of Wistar Rats J. of Immunotherapy 10: 131–140, 1991

    Google Scholar 

  19. Ingram M, Jacques S, Freshwater DB, Techy GB, Shelden CH, Helsper JT: Salvage immunotherapy of malignant glioma. Arch Surg 122: 1483–1486, 1987

    Google Scholar 

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

    Google Scholar 

  21. Merchant RE, Merchant LH, Cook SHS, McVical DW, Young HF: Intralesional infusion of lymphokine-activated killer (LAK) cells and recombinant interleukin-2(rIL-2) for the treatment of patients with malignant brain tumor. Neurosurgery 23: 725–732, 1988

    Google Scholar 

  22. Yoshida S, Tanaka R, Takai N, Ono K: Local administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with malignant brain tumors. Cancer Res 48: 5011–5016, 1988

    Google Scholar 

  23. Dumas-Duport C, Scheithauer B, O'Fallon J, Kelley P: Grading of Astrocytomas: A simple and reproducible method. Cancer 62: 2152–2165, 1988

    Google Scholar 

  24. Burger P, Vogel F, Green S, Strike T: Glioblastoma multiforme and anaplastic astrocytoma. Cancer 56: 1106–1111, 1985

    Google Scholar 

  25. Jeffes E, Schmitz K, Yamamoto R, Tomich J, Beckman M, Nep R, Knauer M: A simple nonisotopicin vitro bioassay for LT and TNF employing sodium fluoride treated L-929 target cells which detects picogram quantities of LT and TNF and is as sensitive as TNF assays done with ELISA methodology, Lymphokine Research 10: 147–151, 1991

    Google Scholar 

  26. Hiserodt JC, Tiangco GJ, Granger GA: The LT system in experimental animals: I. Rapid release of high levels of LT activity from murine lymphocytes during interaction with lectin-treated allogeneic or xenogeneic target cellsin vitro. J Immunol 123: 311–316, 1979

    Google Scholar 

  27. Granger GA, Daynes RA, Runge PE, Prieur AM, Jeffes EWB: Lymphocyte effector molecules and cell-mediated immune reactions. Contemporary Topics in Molecular Immunology 4: 205–241, 1975

    Google Scholar 

  28. Young B, Oldfield E, Markesbery W, Haack D, Tibbs P, McCombs P, Chin H, Maruyama Y, Meacham W: Reoperation for glioblastoma. J Neurosurg 55: 917–921, 1981

    Google Scholar 

  29. Wetzel N, Anderson M, Sheilds T: Pulmonary embolism as a cause of death in the neurosurgical patient. J Neurosurg 17: 664–668, 1960

    Google Scholar 

  30. Kayser-Gatchalian MC, Kayser K: Thrombosis and intracranial tumors. J Neurol 209: 217–224, 1975

    Google Scholar 

  31. Sawaya R, Decourteen-Meyers G, Copeland B: Massive preoperative pulmonary embolism and suprasellar brain tumor: case report and review of the literature. Neurosurgery 15: 566–571, 1984

    Google Scholar 

  32. 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 

  33. Kruse CA, Mitchell DH, Lillehei KO, Johnson SD, McCleary EL, Moore GE, Waldrop S, Mierau W: Interleukin-2 activated lymphocytes from brain tumor patients. Cancer 64: 61–69, 1989

    Google Scholar 

  34. Hiserodt JC, Granger GA: Inhibition of human lymphocyte-mediated mitogen-induced cytotoxicity of murine L-929 cells by heterologous anti-human lymphotoxin anitserain vitro. J Immunol 119: 374–380, 1977

    Google Scholar 

  35. Mazumder A, Grimm EA, Rosenberg SA: Characterization of the lysis of fresh human solid tumors by autologous lymphocytes activatedin vitro with phytohemagglutinin. J Immunol 130: 958–964, 1983

    Google Scholar 

  36. Barba D, Saris SC, Holder C. Rosenberg SA, Oldfield EH: Intratumoral LAK cell and interleukin-2 therapy of human gliomas. J Neurosurg 70: 175–182, 1989

    Google Scholar 

  37. Ingram M, Buckwalter JG, Jacques DB, Freshwater DB, Abts RM, Techy GB, Miyagi K, Shelden CH, Rand RW, English LW: Immunotherapy for recurrent malignant glioma: an interim report on survival. Neurological Res 12: 265–273, 1990

    Google Scholar 

  38. Harris PC, Yamamoto RS, Crane J, Granger GA: The human LT system. X The initial form released by T-enriched lymphocytes is 1500 m.w., associated with small nonlytic components, and can dissociate into alpha, beta, and gamma m.w. classes. J Immunology 126: 2165–2170, 1981

    Google Scholar 

  39. Hiserodt JC, Tiangco GJ, Granger GA: The LT system in experimental animals: II. Physical and immunologic characteristics of molecules with LT activity rapidly release by murine lymphoid cells activated on lectin-coated allogeneic monolayersin vitro. J Immunol 123: 317–324, 1979

    Google Scholar 

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Jeffes, E.W.B., Beamer, Y.B., Jacques, S. et al. Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) Lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA. J Neuro-Oncol 15, 141–155 (1993). https://doi.org/10.1007/BF01053935

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