کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2405043 | 1103010 | 2010 | 8 صفحه PDF | دانلود رایگان |
Clinical and preclinical data indicate that immunotherapeutic interventions could induce immune responses capable of controlling or retard the tumor growth. However, immunotherapies need to be further optimized. We hypothesized that a more effective strategy for tumor eradication is to directly target the tumor microenvironment in order to generate a proinflammatory response and induce a localized antitumor immune response capable of eliminating the tumor cells. Nanoparticles have been proven to be an effective delivery system. In these studies we evaluated conjugated anti-RNEU and anti-CD40 antibodies onto PLA-(poly dl-lactic acid)-biodegradable nanoparticles (PLA-NP) for the induction of antitumor immune responses. The anti-neu/anti-CD40-NP were functional in vitro recognizing RNEU+ tumors and activating dendritic cells. The delivery of anti-neu/anti-CD40-NP but not anti-neu-NP or anti-CD40-NP induced an antitumor response resulting in complete tumor elimination and generation of protective memory responses. The anti-neu/anti-CD40-NP specifically activated an antitumor response against RNEU+ tumors but not against RNEU− tumors. The antitumor immune responses correlate with the induction of a Th1-proinflammatory response, reduction in the number of Tregs within the tumor and activation of a specific cytotoxic response. These results indicate that anti-neu/anti-CD40-NP with immunomodulatory properties are safe and can be used effectively as cancer vaccines strategy for the specific induction of antitumor immune responses.
Journal: Vaccine - Volume 28, Issue 5, 3 February 2010, Pages 1383–1390