Preclinical Studies with JAA-F11 Anti-Thomsen-Friedenreich Monoclonal Antibody for Human Breast Cancer

Abstract

REVIEW BackgroundBreast cancer is one of the most prevalent cancers in women worldwide [1,2] and is the most common cause of cancer deaths in women [2]. The deaths related to breast cancer are not due to the primary tumors, but are due to the metastases to the lungs, brain and bone [3,4]. Therefore, treatment and management to block metastases is an important target for therapy that would improve survival in breast cancer patients.Irregularities in cell adhesion play an important role in cancer progression and metastasis [5]. The Thomsen-Friedenreich antigen (TF-Ag) is the disaccharide, galactose-β1-3N-acetyl galactosamine (Galβ1-3GalNAc) α-O-linked to serine or threonine residues in glycoproteins [6]. It is a tumor-associated antigen, which is covered by other carbohydrate moieties and thus hidden in normal cells, but exposed in cancers such as breast, lung, prostate and bladder [6][7][8][9]. TF-Ag plays a role in cancer cell adhesion and metastasis as a result of interacting with lectins at metastatic sites [10,11]. One particular lectin that interacts with the TF-Ag to establish metastasis is galectin-3. This interaction may provide an explanation for the direct relationship between TF-Ag expression, galectin-3 expression and cancer metastasis and aggression, with patients having elevated galectin-3 levels and tumor cells bearing elevated TF-Ag levels having the most aggressive, metastatic cancers [11,12]. Previous studies proposed that TF-Ag and galectin-3 interaction with galectin-3 mobilization to the endothelial cell surface is involved in the first step of a two-step tumor cell-endothelial cell interaction for tumor adhesion and metastasis [10]. This step is followed by an integrin-mediated orders, please contact: reprints@futuremedicine.com

Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen

“…Early in 1997, Georg F. Springer attempted to induce a T antigen‐specific therapeutic response in humans and successfully immunized breast cancer patients with a T antigen‐positive vaccine containing asialoglycophorin (derived from red blood cell membranes), which resulted in a significant improvement of survival . Furthermore, Heimburg et al certified that JAA‐F11, a monoclonal antibody, could inhibit tumor metastasis, and may be of use as part of an antibody–drug conjugate in cancer therapy . Recently, T antigen vaccination (commensal bacterium Bacteroides ovatus D‐6) has been reported in human acute myelogenous leukemia cell line KG‐1.…”

“…T antigen is expressed in 90% of human cancer types, including precancerous lesions . In addition, T antigen is a disaccharide hidden on normal cells, but selectively exposed on the surface of breast, colon, prostate, and bladder cancer cells . Moreover, the molecular chaperone Cosmc is found hypermethylated in 40% of pancreatic tumors .…”

“…There are three main forms of vaccination: the first form is passive immunization with monoclonal antibodies. Specific monoclonal antibody to T antigen may have greater tumor specificity because T antigen is a disaccharide hidden on normal cells, but can be selectively exposed on the surface of a diverse range of tumor cells . JAA‐F11, a highly specific monoclonal antibody to T antigen, reduces metastasis and prolongs survival in a mouse model .…”

“…JAA‐F11, a highly specific monoclonal antibody to T antigen, reduces metastasis and prolongs survival in a mouse model . Further studies have demonstrated that humanized JAA‐F11 is helpful for immunotherapy and drug conjugation therapy for breast cancer, as it increases the survival rate of patients . The second type is active immunization, for instance, mannan‐coupled MUC‐1 (a carrier protein of T antigen and Tn antigen), which has already been proven effective in phase III trials .…”

Carbohydrate‐based vaccines for oncotherapy

“…Antibodies from sera in TF‐PS B immunized mice bound selectively to TF‐expressing MCF‐7 carcinoma cells in high degree, while decreased in binding to HCT‐116 cells that express less of the TF antigen. And the TF‐specific antibody elicited by TF‐BSA was lower when compared with TF‐PS B …”