Comblike dendrimers containing Tn antigen modulate natural killing and induce the production of Tn specific antibodies

Comblike glycodendrimers were prepared by the chemoselective ligation of cysteine-modified glycopeptides (1-7) with a 3-maleimidopropionate-modified linear synthetic carrier (8). Glycodendrimers bearing mono-, di-, or tri-Tn clusters (9-11) were tested as inhibitors using plant and mammalian lectins. In the former group, the Codium fragile lectin showed moderate discrimination among 9, 10, and 11. In the latter group, A and B isoforms of rat NKR-P1 lectin strongly discriminated between 9 and 10. 10 caused a 4-fold increase in killing of the NK resistant tumor cell lines at concentrations as low as 10(-8) M. Surprisingly, 11 interacted exclusively with the rat NKR-P1B isoform and inhibited efficiently natural killing in both rats and humans, even in the presence of the activating compounds 9 and 10. Dinitrophenol haptenization or influenza virus hemagglutinin T-cell epitope conjugation increased the immunogenicity of the parent compounds and resulted in the production of Tn specific antibodies.