Discovery of a novel highly specific, fully human PSCA antibody and its application as an antibody-drug conjugate in prostate cancer
| Autor: | Xiaojie Chu, Seungmin Shin, Du-San Baek, Liyong Zhang, Alex Conard, Megan Shi, Ye-Jin Kim, Cynthia Adams, Maggie Hines, Xianglei Liu, Chuan Chen, Zehua Sun, Dontcho V. Jelev, John W. Mellors, Dimiter S. Dimitrov, Wei Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | mAbs, Vol 16, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 19420862 1942-0870 1942-0862 |
| DOI: | 10.1080/19420862.2024.2387240 |
| Popis: | Prostate stem cell antigen (PSCA) is expressed in all stages of prostate cancer, including in advanced androgen-independent tumors and bone metastasis. PSCA may associate with prostate carcinogenesis and lineage plasticity in prostate cancer. PSCA is also a promising theranostic marker for a variety of other solid tumors, including pancreatic adenocarcinoma and renal cell carcinoma. Here, we identified a novel fully human PSCA antibody using phage display methodology. The structure-based affinity maturation yielded a high-affinity binder, F12, which is highly specific and does not bind to 6,000 human membrane proteins based on a membrane proteome array assay. F12 targets PSCA amino acids 63–69 as tested by the peptide scanning microarray, and it cross-reacts with the murine PSCA. IgG1 F12 efficiently internalizes into PSCA-expressing tumor cells. The antimitotic reagent monomethyl auristatin E (MMAE)-conjugated IgG1 F12 (ADC, F12-MMAE) exhibits dose-dependent efficacy and specificity in a human prostate cancer PC-3-PSCA xenograft NSG mouse model. This is a first reported ADC based on a fully human PSCA antibody and MMAE that is characterized in a xenograft murine model, which warrants further optimizations and investigations in additional preclinical tumor models, including prostate and other solid tumors. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|