Targeting Tumor Cells by Natural Anti-Carbohydrate Antibodies Using Rhamnose-Functionalized Liposomes

Abstract

Recruitment of antibodies in human immune systems for targeted destruction of tumor cells has emerged as an exciting area of research due to its low occurrence of side effects, high efficacy, and high specificity. The presence of large amounts of anticarbohydrate natural antibodies in human sera has prompted research efforts to utilize carbohydrate epitopes for immune recruitment. Here, we have developed a general strategy for specific targeted destruction of tumor cells based on rhamnose-functionalized liposomes. Tumor cells artificially decorated with rhamnose epitopes were subjected to complement-mediated cytotoxicity in vitro and showed delayed tumor growth in vivo. This study highlights the therapeutic potential for activation of endogenous immune response through cell-surface glycan engineering.

Evidence of Protein Adsorption in Pegylated Liposomes: Influence of Liposomal Decoration

“…By the PEG approach, surface-surface interactions including the aggregation of liposomes and/or adsorption of plasma proteins are reduced [ 13 ] but not totally prevented [ 14 ]. More recently, with the main aim of effectively delivering drugs and improving their therapeutic index and reducing their undesired side effects, liposomes have been tailored by attaching particular components to the outer part of the bilayer like peptides [ 15 , 16 , 17 ] to reach specific targets such as cancer or malaria-infected cells [ 18 , 19 , 20 ]. Among the peptides, the Arginine-Glycine-Aspartate (RGD) triad has been often selected as nanoparticles scaffold for displaying a strong affinity and selectivity to the α V β 3 integrin that is overexpressed in malignant tissues.…”

Multivalent Antibody‐Recruiting Macromolecules: Linking Increased Binding Affinity with Enhanced Innate Immune Killing

“…Nevertheless, as shown in Figure 5, liposomes (FA/rha 1 : 2500) were able to significantly delay tumor growth with minimal toxicity in rhamnose immunized mice, thereby demonstrating the therapeutic benefits of this approach. [61] Recently, the De Geest group published several papers on so-called antibody recruiting polymers (ARPs) in the context of cancer immunotherapy. The first question that was addressed is to what extent polymeric scaffolds that contain multiple antibody-recruiting hapten motifs allow for a more efficient antibody recruitment to the cell surface with prolonged cell surface persistence and efficient induction of innate effector killing.…”

Synthesis of C‐Glycosyl Amino Acid Building Blocks Suitable for the Solid‐Phase Synthesis of Multivalent Glycopeptide Mimics

“…[4,10,11] Another example is the exploitation of the abundance of the circulating anti-L-rhamnose antibodies in human blood, [12,13] that can be recruited using multivalent rhamnose conjugates. [14][15][16][17][18] We reasoned that the development of automated solid phase techniques to generate clusters of (different) carbohydrates would be attractive to rapidly assemble multivalent glycoconjugates. [6] Ponader et al developed a solid-phase synthesis method to obtain homo-and hetero-multivalent glycooligomers using alkyne-functionalized building blocks functionalized by a Cu-catalyzed azide-alkyne [2+3] cycloaddition with mannose, galactose or glucose synthons equipped with an azide.…”