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Keywords = UniCAR T-cell therapy

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19 pages, 4680 KB  
Article
Tackling Prostate Cancer with Theranostic E5B9-Bombesin Target Modules (TMs): From Imaging to Treatment with UniCAR T-Cells
by Liliana R. Loureiro, Susan Pike, Melinda Wuest, Cody N. Bergman, Kira R. JØrgensen, Ralf Bergmann, Anja Feldmann, Frank Wuest and Michael Bachmann
Int. J. Mol. Sci. 2025, 26(6), 2686; https://doi.org/10.3390/ijms26062686 - 17 Mar 2025
Cited by 1 | Viewed by 1683
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 [...] Read more.
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. Full article
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16 pages, 817 KB  
Review
Cell-Based Treatment in Acute Myeloid Leukemia Relapsed after Allogeneic Stem Cell Transplantation
by Martina Canichella and Paolo de Fabritiis
Biomedicines 2024, 12(8), 1721; https://doi.org/10.3390/biomedicines12081721 - 1 Aug 2024
Cited by 1 | Viewed by 4663
Abstract
Allogeneic stem cell transplant (ASCT) remains the only treatment option for patients with high-risk acute myeloid leukemia (AML). Recurrence of leukemic cells after ASCT represents a dramatic event associated with a dismal outcome, with a 2-year survival rate of around 20%. Adoptive cell [...] Read more.
Allogeneic stem cell transplant (ASCT) remains the only treatment option for patients with high-risk acute myeloid leukemia (AML). Recurrence of leukemic cells after ASCT represents a dramatic event associated with a dismal outcome, with a 2-year survival rate of around 20%. Adoptive cell therapy (ACT) is a form of cell-based strategy that has emerged as an effective therapy to treat and prevent post-ASCT recurrence. Lymphocytes are the principal cells used in this therapy and can be derived from a hematopoietic stem cell donor, the patient themselves, or healthy donors, after being engineered to express the chimeric antigen receptor (CAR-T and UniCAR-T). In this review, we discuss recent advances in the established strategy of donor lymphocyte infusion (DLI) and the progress and challenges of CAR-T cells. Full article
(This article belongs to the Special Issue Advances in CAR-T Cell Therapy)
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14 pages, 2239 KB  
Article
Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)
by Nicola Mitwasi, Claudia Arndt, Liliana R. Loureiro, Alexandra Kegler, Frederick Fasslrinner, Nicole Berndt, Ralf Bergmann, Vaclav Hořejší, Claudia Rössig, Michael Bachmann and Anja Feldmann
Int. J. Mol. Sci. 2022, 23(9), 4920; https://doi.org/10.3390/ijms23094920 - 28 Apr 2022
Cited by 6 | Viewed by 4692
Abstract
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), [...] Read more.
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies. Full article
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24 pages, 4317 KB  
Article
Development and Functional Characterization of a Versatile Radio-/Immunotheranostic Tool for Prostate Cancer Management
by Claudia Arndt, Ralf Bergmann, Franziska Striese, Keresztély Merkel, Domokos Máthé, Liliana R. Loureiro, Nicola Mitwasi, Alexandra Kegler, Frederick Fasslrinner, Karla Elizabeth González Soto, Christin Neuber, Nicole Berndt, Noemi Kovács, David Szöllősi, Nikolett Hegedűs, Gyula Tóth, Jan-Philipp Emmermann, Kuzhuvelil B. Harikumar, Tibor Kovacs, Michael Bachmann and Anja Feldmannadd Show full author list remove Hide full author list
Cancers 2022, 14(8), 1996; https://doi.org/10.3390/cancers14081996 - 14 Apr 2022
Cited by 14 | Viewed by 4987
Abstract
Due to its overexpression on the surface of prostate cancer (PCa) cells, the prostate stem cell antigen (PSCA) is a potential target for PCa diagnosis and therapy. Here we describe the development and functional characterization of a novel IgG4-based anti-PSCA antibody (Ab) derivative [...] Read more.
Due to its overexpression on the surface of prostate cancer (PCa) cells, the prostate stem cell antigen (PSCA) is a potential target for PCa diagnosis and therapy. Here we describe the development and functional characterization of a novel IgG4-based anti-PSCA antibody (Ab) derivative (anti-PSCA IgG4-TM) that is conjugated with the chelator DOTAGA. The anti-PSCA IgG4-TM represents a multimodal immunotheranostic compound that can be used (i) as a target module (TM) for UniCAR T cell-based immunotherapy, (ii) for diagnostic positron emission tomography (PET) imaging, and (iii) targeted alpha therapy. Cross-linkage of UniCAR T cells and PSCA-positive tumor cells via the anti-PSCA IgG4-TM results in efficient tumor cell lysis both in vitro and in vivo. After radiolabeling with 64Cu2+, the anti-PSCA IgG4-TM was successfully applied for high contrast PET imaging. In a PCa mouse model, it showed specific accumulation in PSCA-expressing tumors, while no uptake in other organs was observed. Additionally, the DOTAGA-conjugated anti-PSCA IgG4-TM was radiolabeled with 225Ac3+ and applied for targeted alpha therapy. A single injection of the 225Ac-labeled anti-PSCA IgG4-TM was able to significantly control tumor growth in experimental mice. Overall, the novel anti-PSCA IgG4-TM represents an attractive first member of a novel group of radio-/immunotheranostics that allows diagnostic imaging, endoradiotherapy, and CAR T cell immunotherapy. Full article
(This article belongs to the Special Issue Combined CAR T-cell Therapies: A Next Step towards Precision Oncology)
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