The use of autologous stimulated lymphocytes as an adoptive immunotherapy for malignant gliomas: Benefits and limitations

Abstract

Although some reports have indicated that adoptive immunotherapy (AIT) is beneficial for patients with malignant astrocytomas and glioblastomas, however some clinical cases have failed to show AIT's effectiveness as had been expected from in vitro cytotoxicity studies. In this paper, report on our attempts to clarify the benefits and limitations of AIT. To do so, we have investigated the following: the cytotoxic activity of autologous stimulated lymphocytes (ASLs) on glioma cell culture supernatants (GCSs), changes in CT or MRI imagings of patients receiving ASLs for AIT, the pathological findings of specimens obtained from such reoperated AIT patients, and the Kaplan-Meier survival rates of these AIT patients. Ten malignant glioma patients receiving ASLs for their AIT were studied, 6 of these cases involving glioblastomas and 4 presenting malignant astrocytomas. Among these 10 patients, 6 underwent reoperation. With regard to the cytotoxicity of ASL cells and lymphokine-activated killer cells on GCSs from 7 patients and on the glioma cavity cystic fluid from 1 patient, results of a 51chromium release assay revealed that out a total of 10 evaluated GCSs, only 2 showed ASL inhibition. Further, the pathological findings revealed that although some ASLs injected into the cavity of the tumor migrated into the residual glioma tissue, most of the injected ASLs stayed on the surface of the cavity. A complete remission through the use of AIT is very rare and only a single report has been found in the literature. However, we have experienced 2 cases of a recurrent glioblastoma in which, after repeated ASL administrations by a device that provided access to the tumoral cavity, the lesion disappeared. Of these 2 cases, a complete remission was confirmed by MRI in 1 case and by a histological study in the other. In both these cases, the tumoral extension had been local, and the overall mean survival rate from the start of AIT was 51.8 weeks. The best survival-time correlation was seen in cases of a localized tumor, and on identifying the tumor, local AIT administrations increased the length of the patient's survival, the mean survival time of such cases amounting to 85.4 weeks. We thus have concluded that for patients with a localized malignant glioma, a surgical resection and radiotherapy followed by AIT is associated with a longer survival.