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@ARTICLE{Loureiro:300160,
author = {L. R. Loureiro and S. Pike and M. Wuest and C. N. Bergman
and K. R. JØrgensen and R. Bergmann and A. Feldmann$^*$ and
F. Wuest and M. Bachmann$^*$},
title = {{T}ackling {P}rostate {C}ancer with {T}heranostic
{E}5{B}9-{B}ombesin {T}arget {M}odules ({TM}s): {F}rom
{I}maging to {T}reatment with {U}ni{CAR} {T}-{C}ells.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2025-00646},
pages = {2686},
year = {2025},
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.},
keywords = {Prostatic Neoplasms: diagnostic imaging / Prostatic
Neoplasms: therapy / Prostatic Neoplasms: metabolism /
Prostatic Neoplasms: pathology / Male / Humans / Animals /
Bombesin: chemistry / Mice / Positron-Emission Tomography:
methods / Cell Line, Tumor / T-Lymphocytes: immunology /
T-Lymphocytes: metabolism / Xenograft Model Antitumor Assays
/ Receptors, Bombesin: metabolism / Receptors, Bombesin:
antagonists $\&$ inhibitors / Immunotherapy: methods /
Theranostic Nanomedicine: methods / PC-3 Cells / PET (Other)
/ UniCAR T-cell therapy (Other) / bombesin (Other) /
prostate cancer (Other) / theranostics (Other) / Bombesin
(NLM Chemicals) / Receptors, Bombesin (NLM Chemicals)},
cin = {DD01},
ddc = {540},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40141329},
doi = {10.3390/ijms26062686},
url = {https://inrepo02.dkfz.de/record/300160},
}