ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen.
ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen.
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DOI：
10.1158/0008-5472.can-20-1418
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发表时间：
2020-10-15
期刊：
影响因子：
11.2
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Su Y;Zhang X;Bidlingmaier S;Behrens CR;Lee NK;Liu B
Identification of tumor-specific cell surface antigens has proven challenging, as the vast majority of tumor-associated antigens are also expressed in normal tissues. In mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, is incurable, and can be categorized into three histological subtypes: epithelioid, biphasic and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counterselection on normal cells and identified a panel of human antibodies that bind all subtypes of mesothelioma but not normal mesothelium. One of the antibodies, M25, showed high specificity against an antigen we identify here as ALPPL2. Immunohistochemistry on normal human tissues found that ALPPL2 is expressed only on placental trophoblasts but not any other normal tissues. This significant tissue specificity and broad tumor type coverage suggests that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, an ALPPL2-targeted antibody-drug conjugate was developed and demonstrated potent and specific tumor killing in vitro and in vivo against both epithelioid and sarcomatoid mesothelioma. Thus, ALPPL2 belongs to a rare class of cell surface antigens classified as truly tumor-specific and is well suited for therapy development against ALPPL2-expressing tumors.
