Discovery of a novel highly specific, fully human PSCA antibody and its application as an antibody-drug conjugate in prostate cancer
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...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Book |
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Taylor & Francis Group,
2024-12-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_1f085d6811ce4dcda8bde14f50a5302f | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Xiaojie Chu |e author |
| 700 | 1 | 0 | |a Seungmin Shin |e author |
| 700 | 1 | 0 | |a Du-San Baek |e author |
| 700 | 1 | 0 | |a Liyong Zhang |e author |
| 700 | 1 | 0 | |a Alex Conard |e author |
| 700 | 1 | 0 | |a Megan Shi |e author |
| 700 | 1 | 0 | |a Ye-Jin Kim |e author |
| 700 | 1 | 0 | |a Cynthia Adams |e author |
| 700 | 1 | 0 | |a Maggie Hines |e author |
| 700 | 1 | 0 | |a Xianglei Liu |e author |
| 700 | 1 | 0 | |a Chuan Chen |e author |
| 700 | 1 | 0 | |a Zehua Sun |e author |
| 700 | 1 | 0 | |a Dontcho V. Jelev |e author |
| 700 | 1 | 0 | |a John W. Mellors |e author |
| 700 | 1 | 0 | |a Dimiter S. Dimitrov |e author |
| 700 | 1 | 0 | |a Wei Li |e author |
| 245 | 0 | 0 | |a Discovery of a novel highly specific, fully human PSCA antibody and its application as an antibody-drug conjugate in prostate cancer |
| 260 | |b Taylor & Francis Group, |c 2024-12-01T00:00:00Z. | ||
| 500 | |a 10.1080/19420862.2024.2387240 | ||
| 500 | |a 1942-0870 | ||
| 500 | |a 1942-0862 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a Antibody drug conjugate | ||
| 690 | |a fully human antibody | ||
| 690 | |a monomethyl auristatin E | ||
| 690 | |a prostate cancer | ||
| 690 | |a PSCA | ||
| 690 | |a tumor xenograft mouse model | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 690 | |a Immunologic diseases. Allergy | ||
| 690 | |a RC581-607 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n mAbs, Vol 16, Iss 1 (2024) | |
| 787 | 0 | |n https://www.tandfonline.com/doi/10.1080/19420862.2024.2387240 | |
| 787 | 0 | |n https://doaj.org/toc/1942-0862 | |
| 787 | 0 | |n https://doaj.org/toc/1942-0870 | |
| 856 | 4 | 1 | |u https://doaj.org/article/1f085d6811ce4dcda8bde14f50a5302f |z Connect to this object online. |