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Systemic
T cell adoptive immunotherapy of malignant gliomas
Plautz
GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC, Luciano M, Kangisser
DB, Shu S
Department
of Neurological Surgery, Center for Surgery Research, The Cleveland Clinic
Foundation, Ohio 44195, USA
Object.
To determine the feasibility, toxicity, and potential therapeutic benefits of
systemic adoptive immunotherapy, 10 patients with progressive primary or
recurrent malignant glioma received this treatment.
Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of
mediating the regression of experimental brain tumors in animal models.
In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich
source of tumor-immune T cells.
Methods.
In this clinical study, patients were inoculated intradermally with irradiated
autologous tumor cells and granulocyte macrophage-colony stimulating factor as
an adjuvant.
Cells from draining inguinal LNs, surgically resected 7 days after vaccination,
were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and
a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells.
The maximum cell proliferation was 350-fold over 10 days of culture.
The activated cells were virtually all T cells consisting of various proportions
of CD4 and CD8 cells.
These cells were given to patients by intravenous infusion at doses ranging from
9 x 10(8) to 1.5 x 10(11).
There were no Grade 3 or 4 toxicities associated with the treatment.
Following T-cell transfer therapy, radiographic regression that lasted at least
6 months was demonstrated in two patients with recurrent tumors.
One patient demonstrated stable disease that has lasted for more than 17 months.
The remaining patients had progressive disease; however, four of the eight
patients with recurrent tumor remain alive more than 1 year after surgery for
recurrence.
Three patients required intervention with corticosteroid agents or additional
surgery approximately 1 month following cell transfer.
Conclusions.
These intriguing clinical observations warrant further trials to determine
whether this approach can provide therapeutic benefits and improve survival.
PMID:
9647171 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9647171&dopt=Abstract
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