Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Liliana R Loureiro - , Helmholtz-Zentrum Dresden-Rossendorf (HZDR) (Autor:in)
  • Susan Pike - , University of Alberta (Autor:in)
  • Melinda Wuest - , University of Alberta (Autor:in)
  • Cody N Bergman - , University of Alberta (Autor:in)
  • Kira R JØrgensen - , University of Alberta (Autor:in)
  • Ralf Bergmann - , Semmelweis University (Autor:in)
  • Anja Feldmann - , Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Frank Wuest - , University of Alberta (Autor:in)
  • Michael Bachmann - , Institut für Immunologie, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Heidelberg, Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg, Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)

Abstract

Target modules (TMs), intermediate molecules required for UniCAR T-cell therapy, are promising molecules for immunotheranostic approaches. In the current work, we developed TMs containing a monomeric or dimeric form of the antagonist bombesin peptide (BBN2) and assessed their potential for diagnostic imaging using positron emission tomography (PET) as well as immunotherapy in combination with UniCAR T-cells to target and image GRPR expression in prostate cancer. Synthesized monomeric and dimeric BBN2 TMs retained binding to GRPR in vitro. Both BBN2 TMs specifically activated and redirected UniCAR T-cells to eradicate PC3 and LNCaP cancer cells with high efficiency and in a comparable manner. UniCAR T-cells retained a non-exhausted memory phenotype favorable to their persistence and fitness. The 68Ga-labeled BBN2 TMs showed proof-of-target towards GRPR in PC3 and LNCaP xenografts with similar uptake profiles for both BBN2 TMs in dynamic PET experiments. Clearance occurred exclusively through renal elimination. A tremendously increased in vivo metabolic stability of the BBN2 TMs was observed compared to their counterparts without E5B9. Both monomeric and dimeric BBN2 TMs represent novel and promising immunotheranostic tools for application in prostate cancer with exceptionally high in vivo metabolic stability.

Details

OriginalspracheEnglisch
Aufsatznummer2686
FachzeitschriftInternational journal of molecular sciences
Jahrgang26
Ausgabenummer6
PublikationsstatusVeröffentlicht - 17 März 2025
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC11941939
Scopus 105001170713

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Animals, Bombesin/chemistry, Cell Line, Tumor, Humans, Male, Mice, PC-3 Cells, Positron-Emission Tomography/methods, Prostatic Neoplasms/therapy, Receptors, Bombesin/metabolism, T-Lymphocytes/immunology, Xenograft Model Antitumor Assays