2. Academic Validation
  3. An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer

An IgG-based bispecific antibody for improved dual targeting in PSMA-positive cancer

  • EMBO Mol Med. 2021 Feb 5;13(2):e11902. doi: 10.15252/emmm.201911902.
Latifa Zekri 1 2 3,  Fabian Vogt 1,  Lukas Osburg 1,  Stefanie Müller 2 3,  Joseph Kauer 1 2 3,  Timo Manz 1,  Martin Pflügler 1 2 3,  Andreas Maurer 4,  Jonas S Heitmann 2 3,  Ilona Hagelstein 2 3,  Melanie Märklin 2 3,  Sebastian Hörner 1,  Tilmann Todenhöfer 5,  Carsten Calaminus 4,  Arnulf Stenzl 5,  Bernd Pichler 3 4,  Christian la Fougère 3 6,  Marc A Schneider 7,  Hans-Georg Rammensee 1 3,  Lars Zender 3 8,  Bence Sipos 3 8 9,  Helmut R Salih 2 3,  Gundram Jung 1 3
Affiliations

Affiliations

  • 1 Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tuebingen, German Cancer Consortium (DKTK), Partner Site Tuebingen, Tuebingen, Germany.
  • 2 Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany.
  • 3 DFG Cluster of Excellence 2180 "Image-guided and Functional Instructed Tumor Therapy" (IFIT), Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • 4 Department for Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • 5 Department of Urology, University Hospital Tuebingen, Tuebingen, Germany.
  • 6 Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, German Cancer Research Center (DKFZ), Partner Site Tuebingen, Tuebingen, Germany.
  • 7 Translational Research Unit, Thorax Clinic at University Hospital Heidelberg, Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
  • 8 Department of Internal Medicine VIII, University Hospital Tuebingen, Tuebingen, Germany.
  • 9 Department of Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany.
PMID: 33372710 DOI: 10.15252/emmm.201911902
Abstract

The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and on the neovasculature of several other Cancer entities. However, the simultaneous expression of PSMA on both, tumor cells as well as tumor vessels remains unclear, even if such "dual" expression would constitute an important asset to facilitate sufficient influx of effector cells to a given tumor site. We report here on the generation of a PSMA antibody, termed 10B3, which exerts superior dual reactivity on sections of prostate carcinoma and squamous cell carcinoma of the lung. 10B3 was used for the construction of T-cell recruiting bispecific PSMAxCD3 antibodies in Fab- and IgG-based formats, designated Fabsc and IgGsc, respectively. In vitro, both molecules exhibited comparable activity. In contrast, only the larger IgGsc molecule induced complete and durable elimination of established tumors in humanized mice due to favorable pharmacokinetic properties. Upon treatment of three patients with metastasized prostate carcinoma with the IgGsc reagent, marked activation of T cells and rapid reduction of elevated PSA levels were observed.

Keywords

PSMA; bispecific antibody; immunotherapy; lung cancer; prostate cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P991708
    Anti-FOLH1/PSMA And CD3E Antibody