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Discovery of a novel highly specific, fully human PSCA antibody and its application as an antibody-drug conjugate in prostate cancer.
Chu, Xiaojie; Shin, Seungmin; Baek, Du-San; Zhang, Liyong; Conard, Alex; Shi, Megan; Kim, Ye-Jin; Adams, Cynthia; Hines, Maggie; Liu, Xianglei; Chen, Chuan; Sun, Zehua; Jelev, Dontcho V; Mellors, John W; Dimitrov, Dimiter S; Li, Wei.
Afiliación
  • Chu X; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Shin S; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Baek DS; GLPG, Pittsburgh, PA, USA.
  • Zhang L; Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Conard A; GLPG, Pittsburgh, PA, USA.
  • Shi M; Computational and System Biology, School of Medicine, University of Pittsburgh, Pittsburgh, USA.
  • Kim YJ; GLPG, Pittsburgh, PA, USA.
  • Adams C; GLPG, Pittsburgh, PA, USA.
  • Hines M; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Liu X; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Chen C; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Sun Z; GLPG, Pittsburgh, PA, USA.
  • Jelev DV; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Mellors JW; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
  • Dimitrov DS; GLPG, Pittsburgh, PA, USA.
  • Li W; Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.
MAbs ; 16(1): 2387240, 2024.
Article en En | MEDLINE | ID: mdl-39113562
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Inmunoconjugados / Ensayos Antitumor por Modelo de Xenoinjerto / Proteínas Ligadas a GPI / Antígenos de Neoplasias / Proteínas de Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: MAbs Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Inmunoconjugados / Ensayos Antitumor por Modelo de Xenoinjerto / Proteínas Ligadas a GPI / Antígenos de Neoplasias / Proteínas de Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: MAbs Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos