Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in a mouse tumor model

Abstract

In this study, the potential of DNA vaccine by subcutaneously (s.c.) administered block/homo-mixed (B/H) polyplex micelles carrying genes encoding tumor-associated antigen SART3 as well as CD40L and GM-CSF was compared with the intraperitoneal (i.p.) and intravenous (i.v.) administrations or electroporation method. Confocal laser microscopy revealed high localization of polyplexes in groin lymph nodes and local skin tissues after s.c. administration, and in the mesenteric lymph nodes, liver, and spleen after i.p. administration, but not after i.v. administration. Real-time RT-PCR and immunohistochemistry showed transgene expression in the above organs by s.c. and i.p. administered B/H polyplex micelles, but not by the i.v. administration or electroporation. Polyplex-carried DNA vaccines significantly decreased the weight of subcutaneous CT26 tumors in mice compared to the mock (2.9±0.8 vs 6.4±2.6 g, P<0.05 for s.c.; 3.2±1.1 vs 4.7±2.1 g, P<0.05 for i.p. administration). The survival rate was improved by s.c. administration of the DNA vaccine (P<0.05) and by the i.p. administered DNA vaccine (P<0.01) compared with that of the mock controls in mice with peritoneally disseminated CT26 cancer. Such therapeutic effects were not observed by the naked DNA, i.v. administered DNA vaccine or electroporation. CTL and NK cell activities of splenocytes and infiltration of CD11c+ DCs, and CD4+ and CD8a+ T cells into tumor tissues were upregulated in the s.c. administered DNA vaccine group (P<0.05), which was consistent with i.p. administration. No abnormal findings in local injection sites, body weight, or blood examinations were observed by s.c. or i.p. administration of polyplex micelles, whereas proinflammatory cytokine production was minimized in visceral organs with the s.c. administered polyplex-carried DNA vaccine. In conclusion, s.c. administration of B/H polyplex micelles may be a safe and useful modality for DNA vaccination.