Advertisement

Cancer Immunology, Immunotherapy

, Volume 45, Issue 2, pp 77–87 | Cite as

Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2

  • C. A. Kruse
  • Linda Cepeda
  • Betty Owens
  • Stephen D. Johnson
  • John Stears
  • Kevin O. Lillehei
ORIGINAL ARTICLE

Abstract

 For a single-dose toxicity assessment, five patients with recurrent malignant glioma (ages 29–46 years) were treated with intracavitary alloreactive cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2). The trial tested the hypothesis that alloreactive CTL, sensitized to the major histocompatibility complex (MHC) proteins of the patient, offer selective, targeted killing of glioma cells that express MHC. Patient lymphocytes, which also express MHC, were irradiated and placed into CellMax artificial capillary systems with lymphocytes from MHC-disparate donors and CTL developed over a 2- to 3-week period with a low concentration of IL-2. The CTL largely expressed CD3 and CD11a/CD8 markers and lysed targets displaying patient MHC. CTL were implanted into the tumor bed at surgery and a catheter was used for subsequent infusions. Patients received one to five treatment cycles every other month; one cycle generally consisted of two or three CTL infusates administered within a 1- to 2-week period. Different unrelated donors were used for each cycle. Treatment was well tolerated; transient toxicity at grades 1–3 was recorded by NCI Common Toxicity Scale criteria. Two glioblastoma patients have died; one from tumor recurrence locally and the other from recurrence at a site distant from the treatment. Two of the five patients completed five cycles; one anaplastic oligodendroglioma patient shows no evidence of tumor 30 months from the start of immune therapy and an anaplastic astrocytoma patient shows stable disease 28 months after initiation of therapy. One anaplastic oligodendroglioma patient, who dropped the protocol during her second treatment cycle, has no evidence of tumor 28 months after recurrence.

Key words Immunotherapy Cellular therapy Brain tumors Astrocytoma MHC 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • C. A. Kruse
    • 1
  • Linda Cepeda
    • 1
  • Betty Owens
    • 2
  • Stephen D. Johnson
    • 2
  • John Stears
    • 3
  • Kevin O. Lillehei
    • 2
  1. 1.University of Colorado Health Sciences Center, Department of Immunology, Campus Box B184, 4200 East Ninth Avenue, Denver, CO 80262, USA Tel. +1 303 315 5567; Fax +1 303 315 6795 e-mail: carol.kruse@uchsc.eduUS
  2. 2.University of Colorado Health Sciences Center, Department of Surgery, Denver, CO 80262, USAUS
  3. 3.University of Colorado Health Sciences Center, Department of Radiology, Denver, CO 80262, USAUS

Personalised recommendations