Abstract
Abstract The Thomsen-Friedenreich antigen (TF-Ag), a carbohydrate tumor associated antigen, is differentially expressed on carcinomas including those of the breast, colon, and prostate. It is involved in adhesion and metastasis and even low levels of naturally formed antibody to TF-Ag is related to better prognosis. We hypothesize that vaccination to create antibody to TF-Ag may create a survival advantage for patients with TF-Ag+ tumors. The innovation of this work is that both peptide mimics and other novel constructs have been utilized as immunogens. Peptide mimics of TF-Ag, with and without C3d N- terminal peptide constructs and synthetic TF-Ag-Muc 4 constructs with the C3d N- terminal peptide, were prepared to target T cells, and CD21+ splenic B cells and follicular dendritic cells for an increased response and memory B cell production. CD21 is the C3d receptor and MUC-4 is a tumor associated peptide. The immune response was measured using TF-Ag -BSA in enzyme immunoassays. The significance of antibody production to TF-Ag can be seen in the fact that passive immunotherapy with a monoclonal Ab to this Ag decreases lung metastasis and extends survival time of mice bearing breast cancer. The improved survival time is of particular interest because the McAb was not cytotoxic, and the enhanced survival was due to blocking metastasis. A successful vaccine would replicate this inhibition of metastasis and in addition provide cytotoxic effects to improve prognosis.