Suppression of human prostate tumor growth by a unique prostate-specific monoclonal antibody F77 targeting a glycolipid marker.
In our effort to find diagnostic markers and to develop therapeutic approaches for prostate cancer, we have identified an mAb that is capable of binding to a cell surface antigen specifically expressed on both androgen-dependent and androgen-independent prostate cancer cells. Immunohistological studies revealed that this mAb, called F77, stained 112 of 116 primary and 29 of 34 metastatic human prostate cancer specimens. Although the mAb F77 alone directly promotes prostate cancer cell death, it also mediates complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. In addition, mAb F77 can significantly inhibit androgen-independent PC3 and Du145 tumor growth in nude mice. Antigen characterization revealed that mAb F77 recognizes a very small molecular species with glycolipid properties. F77 antigen is concentrated in the lipid-raft microdomains, which serve as platforms for the assembly of associating protein complexes. Thus, the present study indicates that mAb F77 defines a unique prostate cancer marker and shows promising potential for diagnosis and treatment of prostate cancer, especially for androgen-independent metastatic prostate cancer.
Zhang
Geng
G
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA.
Zhang
Hongtao
H
Wang
Qiang
Q
Lal
Priti
P
Carroll
Ann M
AM
de la Llera-Moya
Margarita
M
Xu
Xiaowei
X
Greene
Mark I
MI
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000954:Antigens, Surface / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005434:Flow Cytometry; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000473:pathology*
D000728:Androgens; D017304:Annexin A5; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D017430:Prostate-Specific Antigen