ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen

Area of Science:

• Oncology
• Immunology
• Biochemistry

Background:

• Identifying tumor-specific antigens is difficult due to shared expression with normal tissues.
• Mesothelioma is an incurable cancer with diverse histologic subtypes.
• Novel therapeutic targets with high specificity are needed for mesothelioma.

Purpose of the Study:

• To identify novel, highly specific cell surface antigens for mesothelioma therapy.
• To evaluate the therapeutic potential of targeting the identified antigen.

Main Methods:

• Phage antibody display libraries were used to select antibodies against mesothelioma cells.
• Counterselection on normal tissues ensured antigen specificity.
• Immunohistochemistry (IHC) was performed on normal human tissues.
• An antibody-drug conjugate targeting the antigen was developed and tested.

Main Results:

• A novel antigen, ALPPL2, was identified and found to be highly specific to mesothelioma cells.
• ALPPL2 expression was restricted to placental trophoblasts in normal tissues.
• An ALPPL2-targeted antibody-drug conjugate showed potent, specific killing of mesothelioma cells in vitro and in vivo.
• The antigen demonstrated broad coverage across mesothelioma subtypes.

Conclusions:

• ALPPL2 is a rare, truly tumor-specific cell surface antigen.
• Its high specificity makes it an excellent target for mesothelioma therapy development.
• Targeting ALPPL2 offers a promising new therapeutic strategy for mesothelioma.