Biomaterial-Based Vaccine Induces Regression of Established Intracranial Glioma in Rats

Springer Science and Business Media LLC - Tập 28 - Trang 1074-1080 - 2011
Omar A. Ali1,2,3, Ed Doherty1,2, William J. Bell1, Tracie Fradet1, Jebecka Hudak1, Marie-Therese Laliberte1, David J. Mooney1,2,3, Dwaine F. Emerich1
1InCytu, Inc., Lincoln, USA
2Wyss Institute for Biologically Inspired Engineering, Cambridge, USA
3School of Engineering and Applied Sciences, Harvard University, Cambridge, USA

Tóm tắt

The prognosis for glioma patients is poor, and development of new treatments is critical. Previously, we engineered polymer-based vaccines that control GM-CSF, CpG-oligonucleotide, and tumor-lysate presentation to regulate immune cell trafficking and activation, which promoted potent immune responses against peripheral tumors. Here, we extend the use of this system to glioma. Rats were challenged with an intracranial injection of glioma cells followed (1 week) by administration of the polymeric vaccine (containing GM-CSF, CpG, and tumor-lysate) in the tumor bed. Control rats were treated with blank matrices, matrices with GM-CSF and CpG, or intra-tumoral bolus injections of GM-CSF, CpG, and tumor lysate. Rats were monitored for survival and tested for neurological function. Survival studies confirmed a benefit of the polymeric vaccine as 90% of vaccinated rats survived for >100 days. Control rats exhibited minimal benefit. Motor tests revealed that vaccination protected against the loss of forelimb use produced by glioma growth. Histological analysis quantitatively confirmed a robust and rapid reduction in tumor size. Long-term immunity was confirmed when 67% of survivors also survived a second glioma challenge. These studies extend previous reports regarding this approach to tumor therapy and justify further development for glioma treatment.

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