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Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment.
Loureiro, Liliana R; Hoffmann, Lydia; Neuber, Christin; Rupp, Luise; Arndt, Claudia; Kegler, Alexandra; Kubeil, Manja; Hagemeyer, Christoph E; Stephan, Holger; Schmitz, Marc; Feldmann, Anja; Bachmann, Michael.
Afiliação
  • Loureiro LR; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany. l.loureiro@hzdr.de.
  • Hoffmann L; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Neuber C; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Rupp L; Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Arndt C; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Kegler A; Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Kubeil M; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Hagemeyer CE; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Stephan H; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Australia.
  • Schmitz M; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
  • Feldmann A; Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Bachmann M; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
J Exp Clin Cancer Res ; 42(1): 341, 2023 Dec 15.
Article em En | MEDLINE | ID: mdl-38102692
ABSTRACT

BACKGROUND:

Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression. Aiming to modulate the TME with increased clinical safety and effectiveness, we developed novel small and size-extended immunotheranostic UniCAR target modules (TMs) targeting FAP.

METHODS:

The specific binding and functionality of the αFAP-scFv TM and the size-extended αFAP-IgG4 TM were assessed using 2D and 3D in vitro models as well as in vivo. Their specific tumor accumulation and diagnostic potential were evaluated using PET studies after functionalization with a chelator and suitable radionuclide.

RESULTS:

The αFAP-scFv and -IgG4 TMs effectively and specifically redirected UniCAR T-cells using 2D, 3D, and in vivo models. Moreover, a remarkably high and specific accumulation of radiolabeled FAP-targeting TMs at the tumor site of xenograft mouse models was observed.

CONCLUSIONS:

These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Neoplasias Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Neoplasias Idioma: En Ano de publicação: 2023 Tipo de documento: Article