Carter Teresa, Sterling-Levis Katy, Ow Kim, Doughty Larissa, Hattarki Meghan, Shapira Deborah, Hewish Dean, Kortt Alexander A, Russell Pamela J
School of Clinical Medicine, University of New South Wales, Sydney, Australia.
Cancer Immunol Immunother. 2004 Jun;53(6):533-42. doi: 10.1007/s00262-003-0460-1. Epub 2004 Jan 13.
Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure.
A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1.
Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs.
BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.
单克隆抗体（MAb）用于将药物靶向肿瘤，同时尽量减少对正常组织的暴露。
一种新的抗前列腺癌单克隆抗体BLCA - 38经放射性碘化（I125），并在全身腹腔给药后评估其靶向皮下人前列腺癌（DU - 145）异种移植瘤的能力。作为比较，检测了针对LNCaP - LN3肿瘤的J591单克隆抗体（现处于临床试验阶段）的情况。通过评估注射剂量/克（%ID/g）和异种移植瘤与血液的比例（X/B），在不同时间获得生物分布情况。对异种移植瘤进行了微量放射自显影。与蜂毒素肽毒素偶联后，将BLCA - 38和J591的情况与无关抗体DS - 1进行比较。
125I标记的BLCA - 38和J591单克隆抗体对其相关抗原阳性肿瘤的异种移植瘤定位情况相当，在非肿瘤组织中没有异常定位。F(ab')2和Fab片段的X/B比例有所改善，但异种移植瘤的%ID/g降低，且它们在肾脏、膀胱和胃中蓄积。相比之下，无关抗体的偶联物未显示肿瘤靶向性。微量放射自显影显示单克隆抗体在肿瘤中的蓄积比F(ab')2或Fab更多。
BLCA - 38在体内靶向前列腺癌的效果几乎与J591一样有效。鉴于J591已用于临床，靶向不同抗原的BLCA - 38在前列腺癌的放射免疫闪烁显像和治疗靶向方面具有潜力。
