Dunphy Edward J, McNeel Douglas G
Department of Medicine, Section of Medical Oncology, University of Wisconsin, Madison, Wisconsin 53792, USA.
J Immunother. 2005 May-Jun;28(3):268-75. doi: 10.1097/01.cji.0000158853.15664.0c.
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.
识别合适的前列腺癌相关抗原对于前列腺癌免疫治疗的发展至关重要。Flt3配体是一种树突状细胞的生长和分化因子,在前列腺癌中已显示出适度的临床活性,可能是通过引发抗癌免疫反应。作者此前报道了一项临床试验的结果,在该试验中,一些接受Flt3配体治疗的转移性前列腺癌患者出现了伴有甲状腺特异性抗体的自身免疫性甲状腺功能减退。基于这些发现,作者推测在一些接受Flt3配体治疗的受试者中也可能引发了抗前列腺免疫反应。作者现在报告了在13例接受多个周期Flt3配体治疗的前列腺癌患者中免疫识别的前列腺相关蛋白的鉴定结果。使用正常前列腺cDNA表达文库以及Flt3配体治疗前后受试者的血清,采用改良的SEREX方法鉴定出六种蛋白,与治疗前相比,Flt3配体治疗后针对这些蛋白的IgG免疫反应增强。对一种名为MAD-CaP-5的蛋白的IgG反应在治疗前任何受试者的血清中均未检测到,但在一名受试者治疗后被引发。作者建议可以将MAD-CaP-5作为一种新型前列腺癌抗原进行探索,并且这种方法可用于在任何特定干预后识别免疫识别的蛋白。