The
tumor-associated
carbohydrate Thomsen-Friedenreich antigen (TF-Ag; Galbeta1-3GalNAcalpha-O-Ser/Thr) is overexpressed on the cell surface of several types of
tumor cells, contributing to
cancer cell adhesion and
metastasis to sites containing TF-Ag-binding
lectins. A highly specific
immunoglobulin G(3)
monoclonal antibody (Ab) developed to TF-Ag (JAA-F11) impedes TF-Ag binding to vascular endothelium, blocking a primary metastatic step and providing a survival advantage. In addition, in patients, even low levels of
antibodies to TF-Ag seem to improve prognosis; thus, it is expected that
vaccines generating
antibodies toward TF-Ag would be clinically valuable. Unfortunately, vaccinations with
protein conjugates of
carbohydrate tumor-associated Ags have induced clinically inadequate immune responses. However, immunization using
peptides that mimic
carbohydrate Ags such as Lewis has resulted in both Ab and T-cell responses. Here, we tested the hypothesis that vaccinations with unique TF-Ag
peptide mimics may generate immune responses to TF-Ag
epitopes on
tumor cells, useful for active immunotherapy against relevant
cancers.
Peptide mimics of TF-Ag were selected by phage display biopanning using JAA-F11 and rabbit anti-TF-Ag Ab and were analyzed in vitro to confirm TF-Ag
peptide mimicry. In vitro, TF-Ag
peptide mimics bound to TF-Ag-specific
peanut agglutinin and blocked TF-Ag-mediated rolling and stable adhesion of
cancer cells to vascular endothelium. In vivo, the immunization with TF-Ag-mimicking multiple antigenic
peptides induced TF-Ag-reactive Ab production. We propose that this novel active immunotherapy approach could decrease
tumor burden in
cancer patients by specifically targeting TF-Ag-positive
cancer cells and blocking
metastasis.