Intratumoral dendritic cell vaccin ation elicits potent tumoricidal im munity against malignant glioma in rats

摘要

Dendritic cells(DC)are attractive candidates for innovative cancer immunotherapy by virtu e of their ability to function as powe rful antigen presenting cells and elicit potent antitumor cytotoxic immune r esponses.With the aim of generating antitumor immunity,the authors sought to enhance in vivo tum or antigen presentation by using an i ntratumoral DC vaccination strateg y in the setting of partially irradiated intracranial brain tumo rs.Fisher rats,implanted with 9L gliomas in the right corpus striatum,w ere treated with freshly cultured,unpulsed syngeneic DC inoculated directly into the tumor bed.Intracranially inoculated DCs were found to drain to ipsilateral deep cervical lymph nodes.This was a ssociated with increased local and s ystemic antitumor cytoxicity,as evidenced by robust infiltration of treated tumors with CD4and CD8T ce lls as well as by increased IFN-gamma protein and message levels in in vitr o restimulated splenic lymphocytes.DC therapy resulted in prolonged survival and immunity to s ubsequent intracranial tumor re-ch allenge.These results demonstrate the viability of intratumoral DC vaccination as an effectiv e therapeutic strategy for intracra nial glioma.