Anti-tumor immunity is limited by a number of factors including the lack of fully activated T-cells, insufficient antigenic stimulation and the immune-suppressive tumor microenvironment. We addressed these hurdles by developing a novel class of immunoconjugates, Antibody-Targeted Pathogen-derived Peptides (ATPPs), which were designed to efficiently deliver viral T-cell epitopes to tumors with the aim of redirecting virus-specific memory T-cells against the tumor. ATPPs were generated through covalent binding of mature MHC class I peptides to antibodies specific for cell surface-expressed tumor antigens that mediate immunoconjugate internalization. By means of a cleavable linker, the peptides are released in the endosomal compartment, from which they are loaded into MHC class I without the need for further processing. Pulsing of tumor cells with ATPPs was found to sensitize these for recognition by virus-specific CD8+ T-cells with much greater efficiency than exogenous loading with free peptides. Systemic injection of ATPPs into tumor-bearing mice enhanced the recruitment of virus-specific T-cells into the tumor and, when combined with immune checkpoint blockade, suppressed tumor growth. Our data thereby demonstrate the potential of ATPPs as a means of kick-starting the immune response against “cold” tumors and increasing the efficacy of checkpoint inhibitors.

No abstract

The chemical composition of the leaf resin of Pluchea odorata has been studied from material collected in Tamaulipas, Mexico. It mostly consists of triterpenes and phytosterols and an eudesmane type sesquiterpene. Very small amounts of ten different flavonol aglycones occur, dissolved in this resin; most of them are 6-methoxy compounds. A comparison with previous results on material from El Salvador shows that the latter contains a lesser number of triterpenes and especially of flavonoids, but more sesquiterpenes, while the n-alkane composition varies only quantitatively between both populations.

No abstract

Members of the genus Cistus excrete a leaf resin that consists mainly of terpenoids. This resin also contains methylated flavonoids as aglycones. Rare methyl derivatives of myricetin have been isolated from C. monspeliensis, along with uncommon methyl derivatives of quercetin. Further flavonoids encountered in the leaf resin of this and six further species are methyl derivatives of kaempferol and quercetin, some of apigenin and in one species also of luteolin. The results indicate that there might exist species-specific flavonoid patterns