Sesquiterpene Lactones from Artemisia absinthium. Biotransformation and Rearrangement of the Insect Antifeedant 3α-hydroxypelenolide

Three new compounds, the sesquiterpenes absilactone and hansonlactone and the acetophenone derivative ajenjol, have been isolated from a cultivated variety of Artemisia absinthium. In addition, the major lactone isolated, 3α-hydroxypelenolide, was biotransformed by the fungus Mucor plumbeus affording the corresponding 1β, 10α-epoxide. A cadinane derivative was formed by an acid rearrangement produced in the culture medium, but not by the enzymatic system of the fungus. Furthermore, 3α-hydroxypelenolide showed strong antifeedant effects against Leptinotarsa decemlineata and cytotoxic activity to Sf9 insect cells, while the biotransformed compounds showed antifeedant postingestive effects against Spodoptera littoralis.

A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigen-displaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigen-displaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.