Elsevier

Cellular Immunology

Volume 178, Issue 2, 15 June 1997, Pages 101-107
Cellular Immunology

Regular Article
Treatment of Murine Gliomas by Adoptive Transfer ofex VivoActivated Tumor-Draining Lymph Node Cells

https://doi.org/10.1006/cimm.1997.1140Get rights and content

Abstract

The adoptive transfer of tumor-reactive T lymphocytes has recently been demonstrated to be an effective means for mediating the regression of experimental intracranial fibrosarcomas. In this study, mice bearing syngeneic intracranial GL261 gliomas were cured by the combination of sublethal whole body irradiation followed by the intravenous transfer of tumor-draining lymph node (LN) T cells activated with anti-CD3 or staphylococcal enterotoxin C2 (SEC2). To further identify the functional effector T cell population in the adoptive immunotherapy, LN T cells were separated into two subsets, based on the level of expression of the cell adhesion molecule CD62L (L-selectin). As few as 5 × 105CD62Llowcells could cure the majority of animals, whereas 2 × 106CD62Lhighcells were completely ineffective. Moreover, T cells isolated from advanced intracranial tumors were identified to be predominantly CD62Llow. In contrast, spleens contained a mixture of CD62L low and high cells similar to the transferred cell population. T cells in the glioma site were more actively proliferating than those isolated from the spleen. Mice cured of GL261 tumors demonstrated long-term immunologic memory by rejecting intracranial challenges of the original tumor but not an immunologically distinct tumor. Furthermore, despite infiltration of transferred cells into the intracranial tumors, cured mice did not exhibit any apparent neurologic abnormalities during treatment, prolonged follow-up, or after intracranial tumor rechallenge. This study demonstrates the effective treatment of an intracranial murine glioma by the systemic adoptive transfer of activated tumor-draining LN T cells and selective tumor infiltration by the therapeutically active CD62LlowT cells.

References (35)

  • G.E Plautz et al.

    Cell. Immunol.

    (1996)
  • S.A Rosenberg et al.

    Science

    (1986)
  • A.E Chang et al.

    Cancer Res.

    (1993)
  • P.S Goedegebuure et al.

    J. Clin. Oncol.

    (1939)
  • S Shu et al.

    J. Immunol.

    (1987)
  • H Yoshizawa et al.

    J. Immunol.

    (1991)
  • S Shu et al.

    J. Immunol.

    (1994)
  • B.A Pockaj et al.

    Cancer

    (1994)
  • D.J Cole et al.

    Cancer Immunol. Immunother.

    (1994)
  • Y Sawamura et al.

    J. Neurosurg. Sci.

    (1990)
  • A Fontana et al.

    Semin. Immunopathol.

    (1985)
  • M Maxwell et al.

    J. Neurosurg.

    (1992)
  • T.H Inge et al.

    Cancer Res.

    (1992)
  • L.E French et al.

    J. Cell Biol.

    (1996)
  • M.S Mitchell

    J. Clin. Oncol.

    (1989)
  • W.L Wahl et al.

    J. Immunother.

    (1994)
  • J.J Sussman et al.

    J. Immunother.

    (1995)
  • Cited by (0)

    This work was supported by NIH Grants R01 CA58927 and R37 CA67324 (S.S.)

    2

    To whom correspondence should be addressed at FF5, Center for Surgery Research, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195.

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