Tumor Associated
Antigens (TAAs) are the privileged targets of almost all the
cancer vaccines tested to date. Unfortunately all these
vaccines failed to show a clinical efficacy. The main reason for this failure is the immune tolerance to TAAs that are self-
proteins expressed by normal and
cancer cells. Self-tolerance to TAAs is directed against their dominant rather than against their cryptic
epitopes. The best way to overcome self-tolerance to TAAs would therefore be to target their cryptic
epitopes. However, because of their low HLA-I affinity, cryptic
peptides are non-immunogenic and cannot be used to stimulate an antitumor immune response unless their immunogenicity has been previously enhanced. In this paper we describe a general approach to enhance immunogenicity of almost all the
HLA-B*0702 restricted cryptic
peptides derived from TAAs. It consists in substituting residues at position 1 or 9 of low
HLA-B*0702 affinity cryptic
peptides by an
Alanine or a
Leucine respectively. These substitutions increase affinity of
peptides for
HLA-B*0702. These optimized cryptic
peptides are strongly immunogenic and very importantly CTL they stimulate recognize their native counterparts.TAAs derived optimized cryptic
peptides can be considered as universal antitumor
vaccine since they escape self-tolerance, are immunogenic and are not patient specific.