Inovio Pharmaceuticals Inc (INO)

[johan31]

Another Abstract from Gene Therapy advanced online publication...

This is about Increased Cytokine levels without toxicity

From Sardesai et al.....

Gene Ther. 2014 Oct 2. doi: 10.1038/gt.2014.84. [Epub ahead of print]

Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells.

Bergamaschi C1, Kulkarni V1, Rosati M2, Alicea C1, Jalah R1, Chen S2, Bear J1, Sardesai NY3, Valentin A2, Felber BK1, Pavlakis GN2.



Abstract


Interleukin-15 (IL-15) is a common ?-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15Ra) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8+NK cells, all memory CD8+ T-cell subsets and effector memory CD4+ T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection.Gene Therapy advance online publication, 2 October 2014; doi:10.1038/gt.2014.84.


glta......johan