Tumour-associated glycopeptide antigens and their modification in anticancer vaccines - Carbohydrate Chemistry: Chemical and Biological Approaches - page 522

Scheme 15 Three-component lipopeptide T-cell epitope-MUC1 glycopeptide vaccine
prepared by thioether ligation: a) KI, 8 M urea, 0.1 M NaOAc, NEt 3 /DMF; b) MeOH/cat. NaOMe.
mammary tumour cells showed a significant reduction of tumour burden
compared to non-immunised mice. 66
A third type of three component vaccines was constructed in another
convergent strategy. 68 On the one hand, a spacer-separated conjugate of a
MUC1 glycopeptide and a T-cell epitope (P2) from tetanus toxoid was
synthesised on solid-phase in one linear run and N-terminally equipped
with an acetylated thiol-terminated spacer 54 (see Scheme 15).
After removal of its S-acetyl group, this two-component conjugate 52 was
coupled with the TLR2 ligand lipopeptide Pam 3 CysSKKK-(BrCH 2 CO)Lys-
OH 53 through a chemoselective thioether formation to furnish the three-
component vaccine 54. 68 This fully synthetic vaccine 54 induced a much
stronger immune response in wild-type mice when administered in
phosphate buffer saline (PBS) than when applied together with Freund's
adjuvant (CFA). It has self-adjuvanting properties due to its lipopeptide
portion. The induced antibodies prevailingly were of IgM and IgG1-type
and induced ecient killing of MCF-7 breast tumour cells through acti-
vation of the CDC complex. 68
5 Vaccines obtained by conjugation of glycopeptide
antigens to carrier proteins
The coupling of antigens to carrier proteins in order to arrive at vaccines
for immunological evaluation had been established long before fully