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CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery

Author:
Kheirolomoom, Azadeh, Ingham, Elizabeth S., Mahakian, Lisa M., Tam, Sarah M., Silvestrini, Matthew T., Tumbale, Spencer K., Foiret, Josquin, Hubbard, Neil E., Borowsky, Alexander D., Murphy, William J., Ferrara, Katherine W.
Source:
Journal of Controlled Release 2015 v.220 pp. 253-264
ISSN:
0168-3659
Subject:
adjuvants, breast neoplasms, copper, doxorubicin, drug therapy, mice, nanoparticles, suppressor cells, ultrasonics
Abstract:
Ultrasonic activation of nanoparticles provides the opportunity to deliver a large fraction of the injected dose to insonified tumors and produce a complete local response. Here, we evaluate whether the local and systemic response to chemotherapy can be enhanced by combining such a therapy with locally-administered CpG as an immune adjuvant. In order to create stable, activatable particles, a complex between copper and doxorubicin (CuDox) was created within temperature-sensitive liposomes. Whereas insonation of the CuDox liposomes alone has been shown to produce a complete response in murine breast cancer after 8 treatments of 6mg/kg delivered over 4weeks, combining this treatment with CpG resolved local cancers within 3 treatments delivered over 7days. Further, contralateral tumors regressed as a result of the combined treatment, and survival was extended in systemic disease. In both the treated and contralateral tumor site, the combined treatment increased leukocytes and CD4+ and CD8+ T-effector cells and reduced myeloid-derived suppressor cells (MDSCs). Taken together, the results suggest that this combinatorial treatment significantly enhances the systemic efficacy of locally-activated nanotherapy.
Agid:
5830221