Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer
Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer
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DOI：
10.1007/bf00881818
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发表时间：
1997-04-01
期刊：
影响因子：
--
通讯作者：
Schubiger, PA
中科院分区：
文献类型：
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作者：
Hughes, ODM;Bishop, MC;Schubiger, PA
膀胱移行细胞癌是英国男性癌症死亡的第五大常见原因，大多数患者很早就出现了表面疾病，尽管目前的治疗进展到侵袭性疾病的比例高达20%，这是一种预后很差的疾病。需要更好的局部治疗来限制这种肿瘤的发展。易于通过导管进入膀胱为抗体(Ab)靶向治疗提供了理想的机会，我们先前已经证明，铟-111标记的抗MUC1粘蛋白抗体C595在膀胱内给药后选择性地定位于膀胱肿瘤，我们选择了铜-67作为具有合适物理特性的替代放射标记进行放射免疫治疗。在一种新的体外系统中对膀胱切除标本进行的初步研究表明，C595可以用铜-67重复标记，并且放射免疫结合物既稳定又保持高免疫反应性，并在一名患者中证实了这种结合物在膀胱内给药后定位到肿瘤的能力。在这些研究的基础上，我们现在能够研究铜-67标记的C595在膀胱癌患者的膀胱内给药，以期进行治疗试验。
Transitional cell carcinoma of the bladder is the fifth commonest cause of death from cancer in men in the United Kingdom, Most patients present early with superficial disease, though with current treatment up to 20% progress to invasive disease, which has a poor prognosis. Better local treatments are required to limit this tumour progression. The ease of access to the bladder via a catheter provides the ideal opportunity for antibody (Ab) targeted therapy, We have previously shown that indium-111 labelled anti-MUC1 mucin Ab C595 selectively localises to bladder rumours after intravesical administration, We have selected copper-67 as an alternative radiolabel with suitable physical characteristics for radioimmunotherapy. This communication demonstrates that C595 can be reproducibly labelled with Cu-67 and that the radioimmunoconjugate is both stable and maintains high immunoreactivity, Pilot studies on cystectomy specimens in a novel ex vivo system and in one patient confirmed the ability of this conjugate to localise to tumour after intravesical administration. On the basis of these studies we are now in a position to study the intravesical administration of Cu-67-labelled C595 in patients with bladder cancer with a view to a therapeutic trial.