Human Trophoblast Glycoproteins Defined by Monoclonal Antibody 1D2

Abstract

A cell surface antigen has been defined by a monoclonal antibody 1D2, raised following immunisation with lectin-purified syncytiotrophoblast glycoproteins. 1D2 was nonreactive with any one of 8 common trophoblast proteins in immunodot. Analysis of nonreduced western blots of syncytiotrophoblast microvillous plasma membrane (StMPM) protein indicated that mAb 1D2 was reactive with a series of sialylated proteins with molecular weights of 16–22 kilodaltons. Immunoprecipitates of radiolabelled StMPM protein contained molecules that co-migrated with placental alkaline phosphatase in addition to those identified by western blotting. This set of human trophoblast molecules has not been previously identified by monoclonal antibodies; the antigenicity is widely distributed in human tissues.

The Bispecific Tumor Antigen-Conditional 4–1BB x 5T4 Agonist, ALG.APV-527, Mediates Strong T-Cell Activation and Potent Antitumor Activity in Preclinical Studies

“…These data support the preferential effect of ALG.APV-527, activating infiltrating tumor-specific CD8 T cells. The IHC-based 5T4 expression data presented here confirm reported data showing that 5T4 is mainly expressed in tumors with limited expression in normal healthy tissue [11][12][13][14][15]. Tumor antigen dependent drug localization was investigated in a mouse model, demonstrating that ALG.APV-527 can penetrate tumors, and localize to 5T4-expressing tumor cells.…”

“…5T4 expression was evaluated in both healthy and tumor tissue micro-arrays (TMAs). 5T4 expression in normal healthy tissue was limited and no membrane 5T4 expression was detected in any major organs including the cardiovascular, respiratory, or hepatic systems and in line with previous reports [11][12][13]. Importantly, 5T4 is not expressed in liver (Fig.…”

“…In adults, 5T4 has limited normal tissue expression restricted to some specialized epithelium. In contrast, 5T4 is expressed on numerous solid tumor malignancies including mesothelioma, non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer [11][12][13][14][15]. 5T4 is also highly expressed on tumor initiating stem-cell-like cells [16].…”

“…ALG.APV-527 has been engineered with point mutations to reduce FcR interactions to ensure 5T4-dependent crosslinking, resulting in 5T4conditional 4-1BB activation at sites where both targets are expressed. Since 5T4 expression is highly enriched in tumor compared to healthy tissue [11][12][13][14][15], and 4-1BB expression is primarily inducible by recent TCR or cytokine stimulation on activated immune cells, [6][7][8][9] the overlapping expression pattern of both targets is expected to restrict immune activation by ALG.APV-527 to the TME. Thus, ALG.APV-527 has the potential to enhance anti-tumoral T-cell responses in a highly specific and targeted manner.…”

A single centre phase II trial to assess the immunological activity of TroVax® plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma – the SKOPOS trial

“…14,15 5T4 is a 72 kDa oncofoetal glycoprotein that is expressed in many solid tumors but shows minimal or no expression in normal tissues. 16 We have shown that 5T4 is widely expressed in mesothelioma tissue and on mesothelioma cell lines. 17 Unlike WT-1 and mesothelin, which display subtype-restricted expression, often excluding the more aggressive sarcomatoid variant, 5T4 expression has been shown in all MPM subtypes.…”