Thomsen-Friedenreich antigen (TF-Ag) is expressed in many
carcinomas, including those of the breast, colon, bladder, and prostate. TF-Ag is important in adhesion and
metastasis and as a potential
immunotherapy target. We hypothesized that passive transfer of JAA-F11, an anti-TF-Ag
monoclonal antibody, may create a survival advantage for patients with TF-Ag-expressing
tumors by cytotoxicity, blocking of
tumor cell adhesion, and inhibition of
metastasis. This was tested using in vitro models of
tumor cell growth; cytotoxicity assays; in vitro, ex vivo, and in vivo models of
cancer metastasis; and, finally, in vivo effects in mice with metastatic
breast cancer. Unlike some anti-TF-Ag
antibodies, JAA-F11 did not enhance
breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1
tumor cells through
complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of
metastasis that involve the adhesion of human
breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60) in in vitro static adhesion models, in a perfused ex vivo model, and in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1
breast tumors and caused a > 50% inhibition of lung
metastasis.