SYSTEMIC T-CELL ADOPTIVE IMMUNOTHERAPY OF MALIGNANT GLIOMAS

Object. To determine the feasibility, toxicity, and potential therapeu tic benefits of systemic adoptive immunotherapy, 10 patients with prog ressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capa ble of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vacc ine site are a rich source of tumor-immune T cells. Methods. in this c linical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating f actor as an adjuvant. Cells from draining inguinal LNs, surgically res ected 7 days after vaccination, were stimulated sequentially with stap hylococcal 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 cell s were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infus ion at doses ranging from 9 X 10(8) to 1.5 X 10(11). There were no Gra de 3 or 4 toxicities associated with the treatment. Following T-cell t ransfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient d emonstrated stable disease that has lasted for more than 17 months. Th e remaining patients had progressive disease however, four of the eigh t patients with recurrent tumor remain alive more than 1 year after su rgery for recurrence. Three: patients required intervention with corti costeroid agents or additional surgery approximately 1 month following cell transfer. Conclusions. These intriguing clinical observations wa rrant further trials to determine whether this approach can provide th erapeutic benefits and improve survival.