Recent Advances in Design of Immunogenic and Effective Naked DNA Vaccines Against Cancer
Daniela Fioretti, Sandra Iurescia and Monica Rinaldi
Affiliation: Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere 100 - 00133 Rome, Italy.
Keywords: Cancer, DNA vaccine, epitope, genetic adjuvant, immunotherapy, T cell help, targeting, tumour antigens.
A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated
and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective
against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity
and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required
to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific
references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and
relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific
transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory
pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines
with improved specificity, such as mesothelin and hTERT, are also discussed. Lastly, we review novel patents on
the use of genetic immunomodulators, such as “universal” T helper epitopes derived from tetanus toxin, E. coli heat labile
enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL-
21 to amplify immunity against cancer.
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