T cell adoptive immunotherapy of newly diagnosed gliomas

Gregory E. Plautz, David W. Miller, Gene H. Barnett, Glen H.J. Stevens, Scott Maffett, Julian Kim, Peter A. Cohen, Suyu Shu

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Patients with newly diagnosed gliomas were treated with adoptive transfer of ex vivo activated T lymphocytes, derived from lymph nodes (LNs) draining autologous tumor vaccines, to determine the long-term toxicity of this treatment. Twelve consecutive patients were enrolled: 2 with grade II astrocytoma, 4 with anaplastic gliomas, and 6 with glioblastoma multiforme. Patients were injected intradermally with short-term cultured autologous irradiated tumor cells, admixed with granulocyte macrophage colony- stimulating factor, to stimulate draining LNs. The LN cells were activated with staphylococcal enterotoxin A for 48 h and then cultured in medium containing interleukin 2 for an additional 6-8 days and subsequently transferred i.v. to the patients. The number of cells obtained from the LNs ranged from 9 x 107 to 1.1 x 109, and the median cell proliferation was 41- fold. The dose of T cells infused ranged from 0.6 to 5.5 x 1010 with a median of 1.1 x 1010, the majority of which were CD 4+ (mean, 71%). The entire treatment was performed as outpatient therapy and was associated with a toxicity of grade 2 or less, consisting mainly of fever, nausea, and myalgias during the first 24 h. There were no indications of late adverse events from this treatment even among three patients with follow-up greater than 2 years post T cell transfer. Moreover, four patients demonstrated partial regression of residual tumor. This Phase I clinical trial of adoptive immunotherapy for patients with newly diagnosed malignant gliomas demonstrates feasibility, lack of long-term toxicity, and several objective clinical responses.

Original languageEnglish (US)
Pages (from-to)2209-2218
Number of pages10
JournalClinical Cancer Research
Volume6
Issue number6
StatePublished - Jun 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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