A study led by Filipa Marcelo, post-doc researcher at the Bio-NMR group led by Eurico Cabrita at UCIBIO in Lisbon, reports, for the first time, a strategy to elucidate the key structural elements required to design an efficient anticancer vaccine. The work was published in Journal of the American Chemical Society in September 2015.
Every living cell on Earth is covered by a complex pattern of sugars. Alteration of the sugar pattern of the MUC1 glycoprotein is a common characteristic of different types of cancer. In a normal tissue, MUC1 is decorated by complex sugars, while in cancer cells new sugar moieties, such as the Tn motif, are now exposed to the immune system and can be used as antigens to generate specific antibodies to directly probe cancer cells.
Filipa Marcelo explains that “in this work we report a well-defined protocol, which can be employed, in a general manner to determine the minimal structural features that modulate antigen-antibody specificity”. These findings are important to simplify the development of a more accurate anticancer vaccine.
This research work, done in collaboration with researchers from France, Japan and Spain, combines a multidisciplinary approach: synthesis of MUC1 antigens, generation of antibodies, microarrays assays (MA) and saturation transfer difference NMR (STD-NMR), with the main goal to decipher, in tumor-MUC1 antigen structure, which are the main atoms relevant for antibody interaction. The combination of MA and STD-NMR provides a unique opportunity to investigate the functional significance of tumor-associated MUC1 antigens, giving detailed information for the design of cancer vaccines.
“In fact, our work constitutes one of the few reports where the molecular determinants of antigen-antibody recognition were deeply addressed, that will be naturally extended to other tumor-associated MUC1 antigens, than Tn-antigen, with the main objective to design sugar-based anticancer vaccine to be tested in vivo”, says Filipa Marcelo.