Intratumoral dendritic cell vaccination elicits potent tumoricidal immunity against malignant glioma in rats.
Dendritic cells (DC) are attractive candidates for innovative cancer immunotherapy by virtue of their ability to function as powerful antigen presenting cells and elicit potent antitumor cytotoxic immune responses. With the aim of generating antitumor immunity, the authors sought to enhance in vivo tumor antigen presentation by using an intratumoral DC vaccination strategy in the setting of partially irradiated intracranial brain tumors. Fisher rats, implanted with 9L gliomas in the right corpus striatum, were 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 associated with increased local and systemic antitumor cytoxicity, as evidenced by robust infiltration of treated tumors with CD4 and CD8 T cells as well as by increased IFN-gamma protein and message levels in in vitro restimulated splenic lymphocytes. DC therapy resulted in prolonged survival and immunity to subsequent intracranial tumor re-challenge. These results demonstrate the viability of intratumoral DC vaccination as an effective therapeutic strategy for intracranial glioma.
Ehtesham
Moneeb
M
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Kabos
Peter
P
Gutierrez
Mervin A R
MA
Samoto
Ken
K
Black
Keith L
KL
Yu
John S
JS
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells / Q000637:transplantation*; D004195:Disease Models, Animal; D005910:Glioma / Q000276:immunology* / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014611:Vaccination / Q000379:methods