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Article

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

by
Liliana R. Loureiro
1,†,
Susan Pike
2,3,†,
Melinda Wuest
2,3,
Cody N. Bergman
2,
Kira R. JØrgensen
2,
Ralf Bergmann
4,
Anja Feldmann
1,5,6,7,
Frank Wuest
2,3,* and
Michael Bachmann
1,5,6,7,*
1
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany
2
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
3
Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB T6G 2E1, Canada
4
Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary
5
German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
6
National Center for Tumor Diseases Dresden (NCT/UCC), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
7
Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(6), 2686; https://doi.org/10.3390/ijms26062686
Submission received: 6 February 2025 / Revised: 12 March 2025 / Accepted: 15 March 2025 / Published: 17 March 2025
(This article belongs to the Special Issue Novel Strategies in the Development of New Therapies, Drug Substances and Drug Carriers, 3rd Edition)
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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: UniCAR T-cell therapy; bombesin; theranostics; prostate cancer; PET UniCAR T-cell therapy; bombesin; theranostics; prostate cancer; PET
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MDPI and ACS Style

Loureiro, L.R.; Pike, S.; Wuest, M.; Bergman, C.N.; JØrgensen, K.R.; Bergmann, R.; Feldmann, A.; Wuest, F.; Bachmann, M. Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells. Int. J. Mol. Sci. 2025, 26, 2686. https://doi.org/10.3390/ijms26062686

AMA Style

Loureiro LR, Pike S, Wuest M, Bergman CN, JØrgensen KR, Bergmann R, Feldmann A, Wuest F, Bachmann M. Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells. International Journal of Molecular Sciences. 2025; 26(6):2686. https://doi.org/10.3390/ijms26062686

Chicago/Turabian Style

Loureiro, Liliana R., Susan Pike, Melinda Wuest, Cody N. Bergman, Kira R. JØrgensen, Ralf Bergmann, Anja Feldmann, Frank Wuest, and Michael Bachmann. 2025. "Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells" International Journal of Molecular Sciences 26, no. 6: 2686. https://doi.org/10.3390/ijms26062686

APA Style

Loureiro, L. R., Pike, S., Wuest, M., Bergman, C. N., JØrgensen, K. R., Bergmann, R., Feldmann, A., Wuest, F., & Bachmann, M. (2025). Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells. International Journal of Molecular Sciences, 26(6), 2686. https://doi.org/10.3390/ijms26062686

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