Antigen-specific IgG elicited in subjects with prostate cancer treated with flt3 ligand.
Identifying appropriate prostate cancer-associated antigens is critical to the development of immunologic treatments for prostate cancer. Flt3 ligand, a growth and differentiation factor for dendritic cells, has shown modest clinical activity in prostate cancer, presumably by eliciting anti-cancer immune responses. The authors previously reported the results of a clinical trial in which some patients with metastatic prostate cancer treated with flt3 ligand developed autoimmune hypothyroidism with thyroid-specific antibodies. Given these findings, the authors hypothesized that anti-prostate immune responses might also have been elicited in some subjects treated with flt3 ligand. The authors now report the identification of prostate-associated proteins immunologically recognized in 13 prostate cancer patients treated with multiple cycles of flt3 ligand. Using a normal prostate cDNA expression library, and sera from subjects before and after treatment with flt3 ligand, a modified SEREX approach was used to identify six proteins to which IgG immune responses were augmented after flt3 ligand treatment compared with pretreatment. IgG responses to one protein, MAD-CaP-5, were not detectable in any of the subjects' sera before treatment but were elicited after therapy in one subject. The authors suggest that MAD-CaP-5 could be explored as a novel prostate cancer antigen, and that this approach can be used to identify immunologically recognized proteins following any specific intervention.
Dunphy
Edward J
EJ
Department of Medicine, Section of Medical Oncology, University of Wisconsin, Madison, Wisconsin 53792, USA.
McNeel
Douglas G
DG
D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000627:therapeutic use*; D011467:Prostate / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D008565:Membrane Proteins; C504238:ZNFX1 protein, human; C084881:flt3 ligand protein