PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31171773.
- Also identified by DOI 10.1038/s41467-019-10127-x and PMC identifier 6554295.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3<sup>+</sup> cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an 'inside-out' externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3<sup>+</sup> tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.
Medical subject headings
- Antibody-Dependent Cell Cytotoxicity
- Antineoplastic Agents, Immunological
- Carcinoma, Hepatocellular
- Cytophagocytosis
- Hepatocytes
- Liver Neoplasms
- Neoplasm Proteins
- Protein Tyrosine Phosphatases
- Tumor Microenvironment