Intracranial administrations of single or multiple source allogeneic cytotoxic T lymphocytes: chronic therapy for primary brain tumors

Summary

Previous investigations by our group demonstrated the efficacy of single source allogeneic cytotoxic T lymphocytes (CTLs) given multiple times in reducing or curing tumor burden in the rat 9L gliosarcoma model. In this study, the lack of toxicity to normal brain when single source allogeneic CTLs were intracranially administered multiple times is documented. Additionally, the efficacy and lack of toxicity of allogeneic CTLs from multiple sources, each given once is documented. CTLs sensitized to Fischer antigen were prepared from major histocompatibility complex incompatible DA, PVG, Sprague-Dawley and Wistar-Furth rat lymphocytes. CTLs from multiple donors were administered one time each to Fischer rats bearing established 9L tumor at staggered intervals over a two week period and survival was monitored in relation to a sham treated group. Additional groups of nontumor-bearing rats received either multiple source allogeneic CTLs or single source DA anti Fischer CTLs in the same treatment regimen. Histological evaluation of the nontumor-bearing brains receiving either single or multiple source allogeneic CTL infusions showed minimal localized brain damage confined to the cannulation tract. No neuronal loss or inflammatory reaction was seen either adjacent to or remote from the administration site. Brains from the long-term survivors of the tumor-bearing animals showed no residual neoplasm; the instillation site had focal sterile abscesses; gliosis and neuronal loss did not extend into adjacent brain. The safety and potential of chronic, local allogeneic CTL administration, derived from multiple donors, as adjuvant local therapy for brain tumors was demonstrated.