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Clinical Trials |
Center for Surgery Research [G. E. P., S. M. , J. K., P. A. C., S. S.] and Department of Neurological Surgery [D. W. M., G. H. B., G. H. J. S.], The Cleveland Clinic Foundation, Cleveland, Ohio 44195
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.
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