Rational for clinical use of MSC-Cyt for glioblastoma
Glioblastoma is a devastating disease with a high medical need for new therapeutic approaches. The incidence of glioblastoma is 3,19 per 100.000 in the USA. Only few patients survive for more than 2.5 years, 5 year survival is less than 5%.
Interleukins have been investigated as promising anti-cancer therapy. But there have been limitations in vivo like toxic side effects and low stimulating effects on immune cells when applied systemically. To overcome these limitations interleukins alone and interleukin combinations could be transduced into human mesenchymal stem cells (hMSCs) which offer tumor site-specific expression of interleukins because of homing capacities. Interleukin IL-7, -12 are proinflammatory cytokines that trigger innate and adaptive immune responses. IL-7 combined with IL-12 was stably transduced in hMSCs. MSC-IL7/IL12 (MSC-Cyt) were tested in in vitro assays. They elicitated a strong Interferon γ, TNF α response from human monocytes and promoted NK cell activity.
In an orthotopic glioblastoma model mouse brain was inoculated with glioblastoma cells (Gl261). 5 days after beginning of tumor growth MSC-Cyt were injected twice (day 5 and 10) into the tumor. 50% of the animals in the treatment group showed an ongoing complete remission after 3 months (Pict. 1) After rechallenge with tumor cells MSC-Cyt promoted antitumor immunity analogous to tumor vaccines and no animal showed tumor growth (Pict. 2)