RESUMO
The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4'F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.
RESUMO
Regarding its many roles for lead optimization and drug development, fluorine will definitely continue to be of major importance in medicinal chemistry. With safe and selective fluorinating agents at hands, the use of fluorinated compounds has become routine in pharmaceutical and material sciences and many of the well-appreciated organofluorine inductive effects are now understood. In contrast, our knowledge of how fluorine affects binding affinity and selectivity of proteins and antibodies at the molecular level is by far less advanced. Thus, applications of fluorinated haptens and antigens in the mapping of binding epitopes for various antibodies of diagnostic and therapeutic relevance, as well as for the generation of immune modulating agents and ligands with enhanced T cell affinity are reviewed. Moreover, recent examples of vaccines against cocaine and cancer based on selectively fluorinated antigens with improved antigenic properties are presented.
