Electrotransfer of IL-15/IL-15Rα Complex for the Treatment of Established Melanoma

Autor: Shawna A. Shirley, Niculina I. Burcus, Richard Heller, Cathryn Lundberg
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Cancers, Vol 12, Iss 3072, p 3072 (2020)
Journal for Immunotherapy of Cancer
Volume 12
Issue 10
ISSN: 2072-6694
DOI: 10.3390/cancers12103072
Popis: Gene electrotransfer (GET) is a safe, reliable, and effective method of delivering plasmid DNA (pDNA) to solid tumors. GET has been previously used to deliver interleukin-15 (IL-15) to mouse melanoma, resulting in long-term tumor regression and the survival of a percentage of treated animals after challenge. To enhance this effect, we evaluated modulating the expression levels of IL-15 and co-expressing its receptor, IL-15R&alpha
GET was used to deliver plasmids encoding IL-15 and IL-15R&alpha
to established B16.F10 tumors on days 0, 4, and 7. Two delivery protocols that yielded different expression profiles were utilized. Mice that were tumor-free for 50 days were then challenged with B16.F10 cells on the opposite flank and monitored for an additional 50 days. The amount of IL-15 expressed and the presence or absence of IL-15R&alpha
in the treated tumors did not significantly affect the tumor regression and long-term survival. Upon challenge, however, low levels of IL-15 were more protective and resulted in a greater production of anti-tumor cytokines such as IFN-&gamma
and MIP-1&beta
and a greater amount of CD11b+ and CD3e+ cells infiltrating tumors. While mice with high levels of IL-15 showed CD11b+ and CD3e+ cell infiltrate, there was a substantial presence of NK cells that was absent in other treated groups. We can conclude that the level of IL-15 expressed in tumors after GET is an important determinant of the therapeutic outcome, a finding that will help us finetune this type of therapy.
Databáze: OpenAIRE
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