前列腺癌（PCa）是最常見的惡性腫瘤，影響全球超過14%的男性，并占男性癌癥相關死亡的約1/14[1]。轉移性前列腺癌（PCa）至今仍缺乏有效治療手段，臨床需求巨大，亟待新的藥物靶點與治療策略。細胞膜蛋白STEAP1（six-transmembrane epithelial antigen of prostate 1）在超過85%的前列腺腫瘤中呈高表達，而正常組織幾乎不表達，使其成為極具潛力的精準靶向分子[2]。
近岸蛋白全新上線STEAP1靶點蛋白產品，依托公司專業的多次跨膜蛋白表達與純化平臺，提供去垢劑和VLP形式的高質量六次跨膜全長STEAP1抗原，均由人源細胞表達，并經ELISA和BLI驗證具備良好生物活性，適用于抗體免疫、篩選及質量控制等關鍵環節，助力新靶點抗體藥物研發高效推進。
STEAP1簡介
STEAP1屬于STEAP蛋白家族[3]，該家族包含STEAP1-4四個成員，均為具有六個跨膜結構域、細胞質N端的多跨膜蛋白。STEAP1作為金屬還原酶，可將鐵離子還原，支持細胞代謝與增殖。與STEAP2-4不同，STEAP1缺乏細胞質氧化還原酶結構域[4]，但其分子構型可形成同源三聚體或與其他STEAP蛋白形成異源三聚體，從而增強其活性并可能影響細胞間通訊。
圖1. STEAP靶點蛋白的結構[5]
STEAP1的五大治療策略[2]
STEAP1已成為PCa治療的有效靶點，相關策略正在積極探索（表1）。目前針對STEAP1的方法包括T細胞雙特異抗體、嵌合抗原受體（CAR）T細胞療法、抗體-藥物偶聯物（ADC）以及癌癥疫苗等。這些療法旨在直接清除表達STEAP1的腫瘤細胞或動員免疫細胞增強抗腫瘤反應（圖2）。
表1. STEAP1的五大治療策略[2]
圖2. 靶向STEAP1高表達腫瘤的多種免疫治療策略[2]
靶向STEAP1藥物在研情況
AMG-509是安進開發的STEAP1/CD3雙特異性抗體，在轉移性去勢抵抗性前列腺癌（mCRPC）患者中展現出良好療效：PSA50達49%，ORR達41%，DCR達79%，腫瘤縮小明顯，安全性可控。隨著三期臨床啟動，AMG 509有望成為前列腺癌免疫治療的新突破口。截至2025年7月9日，藥渡數據庫顯示國外已有10家公司圍繞STEAP1靶點開展不同階段的臨床研究，國內也有3家相關研發管線。
表2. 靶向STEAP1藥物進展
基于專業的多次跨膜蛋白技術平臺，近岸蛋白開發出高質量全長STEAP1蛋白，具有正確的天然構象和穩定的生物學活性，是STEAP1靶向藥物開發重要的蛋白工具。
部分數據展示
ELISA驗證
Immobilized Anti-Human STEAP1 Antibody (VAN_bio, Research Grade) (Cat#NC338) at 2μg/ml (100 μl/well) can bind Recombinant Human STEAP1 (N-Flag, C-6His) (Cat#C48A-A).The EC50 of Recombinant Human STEAP1 (N-Flag, C-6His)(Cat#C48A-A) is 79.33ng/ml.
BLI驗證
Loaded Anti-Human STEAP1 Antibody (VAN_bio, Research Grade) (Cat#NC338) on Pro-A Biosensor, can bind Recombinant Human STEAP1 (N-Flag, C-6His) (Cat#C48A-A) with an affinity constant of 5.89 nM as determined in BLI assay.
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Recombinant Human STEAP1(N-Twin-Strep, C-10His) |
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多次跨膜蛋白相關產品
參考文獻
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[7]Kelly, William K., et al. "Xaluritamig, a STEAP1× CD3 XmAb 2+ 1 immune therapy for metastatic castration-resistant prostate cancer: results from dose exploration in a first-in-human study." Cancer discovery 14.1 (2024): 76-89. DOI: 10.1158/2159-8290.CD-23-0964.
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[11]Danila, Daniel C., et al. "Phase I study of DSTP3086S, an antibody-drug conjugate targeting six-transmembrane epithelial antigen of prostate 1, in metastatic castration-resistant prostate cancer." Journal of Clinical Oncology 37.36 (2019): 3518-3527. DOI: 10.1200/JCO.19.00646.
[12]Stein, Mark N., et al. "Prime-boost immunotherapeutic trial in men with biochemical recurrence after definitive local therapy for prostate cancer." (2023): TPS5119-TPS5119. DOI:10.1200/JCO.2023.41.16_suppl.TPS5119.
[13]Carrasquillo, Jorge A., et al. "Imaging patients with metastatic castration-resistant prostate cancer using 89Zr-DFO-MSTP2109A anti-STEAP1 antibody." Journal of Nuclear Medicine 60.11 (2019): 1517-1523. DOI: 10.2967/jnumed.118.222844.