Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11.
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.
Heimburg
Jamie
J
Department of Microbiology and Immunology, The University at Buffalo, Buffalo, NY 14214, USA.
Yan
Jun
J
Morey
Susan
S
Glinskii
Olga V
OV
Huxley
Virginia H
VH
Wild
Linda
L
Klick
Robert
R
Roy
Rene
R
Glinsky
Vladislav V
VV
Rittenhouse-Olson
Kate
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; C016467:Thomsen-Friedenreich antigen