| Abstract: |
We recently developed an efficient strategy based on a fully synthetic dendrimeric carbohydrate display (multiple antigenic glycopeptide; MAG) to induce anticarbohydrate antibody responses for therapeutic vaccination against cancer. Here, we show the superior efficacy of the MAG strategy over the traditional keyhole limpet hemocyanin glycoconjugate to elicit an anticarbohydrate IgG response against the tumor-associated Tn antigen. We highlight the influence of the aglyconic carrier elements of such a tumor antigen for their recognition by the immune system. Finally, we additionally developed the MAG system by introducing promiscuous HLA-restricted T-helper epitopes and performed its immunological evaluation in nonhuman primates. MAG:Tn vaccines induced in all of the animals strong tumor-specific anti-Tn antibodies that can mediate antibody-dependent cell cytotoxicity against human tumor. Therefore, the preclinical evaluation of the MAG:Tn vaccine demonstrates that it represents a safe and highly promising immunotherapeutic molecularly defined tool for targeting breast, colon, and prostate cancers that express the carbohydrate Tn antigen. |
| Keywords: |
controlled study; unclassified drug; drug efficacy; nonhuman; drug targeting; antigen expression; animal cell; mouse; animals; mice; animal tissue; cancer immunotherapy; breast cancer; protein targeting; animal experiment; antineoplastic activity; cytotoxicity; cercopithecus aethiops; tumor antigen; mice, inbred balb c; prostate cancer; immunoglobulin g; cancer vaccine; cancer vaccines; colon cancer; antibody response; antigen recognition; vaccination; epitope; antibody specificity; t-lymphocytes, helper-inducer; primate; macaca; epitopes, t-lymphocyte; antibodies, neoplasm; hla antigen; antigens, tumor-associated, carbohydrate; carbohydrate antigen; tn antigen; glycopeptides; helper cell; keyhole limpet hemocyanin; hemocyanin; immunoconjugates; immunotherapy, active; humans; male; female; priority journal; article; keyhole limpet hemocyanin glycoconjugate; keyhole limpet hemocyanin tn antigen conjugate; multiple antigenic glycopeptide tn antigen vaccine; multiple antigenic glycopeptide tn(hs)3 pv antigen vaccine; multiple antigenic glycopeptide tn(s)3 pv antigen vaccine; multiple antigenic glycopeptide tn3 tt antigen vaccine
|
