IgG-based B7-H3xCD3 bispecific antibody for treatment of pancreatic, hepatic and gastric cancer.

Autor:	Lutz MS; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany., Zekri L; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.; Department of Immunology, Eberhard Karls Universität Tübingen, Tuebingen, Germany., Weßling L; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany., Berchtold S; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.; Department of Internal Medicine VIII, Medical Oncology & Pneumology, University Hospital Tübingen, Tuebingen, Germany.; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Tübingen, Germany., Heitmann JS; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany., Lauer UM; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.; Department of Internal Medicine VIII, Medical Oncology & Pneumology, University Hospital Tübingen, Tuebingen, Germany.; German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Tübingen, Germany., Jung G; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.; Department of Immunology, Eberhard Karls Universität Tübingen, Tuebingen, Germany., Salih HR; Department of Internal Medicine, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tuebingen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Apr 14; Vol. 14, pp. 1163136. Date of Electronic Publication: 2023 Apr 14 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1163136
Abstrakt:	T cell-based immunotherapy has significantly improved treatment options for many malignancies. However, despite these and other therapeutic improvements over the last decades, gastrointestinal cancers, in particular pancreatic, hepatic and gastric cancer, are still characterized by high relapse rates and dismal prognosis, with an accordingly high unmet medical need for novel treatment strategies. We here report on the preclinical characterization of a novel bispecific antibody in an IgG-based format termed CC-3 with B7-H3xCD3 specificity. In many cancer entities including pancreatic, hepatic and gastric cancers, B7-H3 (CD276) is overexpressed on tumor cells and also on the tumor vasculature, the latter allowing for improved access of immune effector cells into the tumor site upon therapeutic targeting. We demonstrate that CC-3 induces profound T cell reactivity against various pancreatic, hepatic and gastric cancer cell lines as revealed by analysis of activation, degranulation and secretion of IL2, IFNγ as well as perforin, resulting in potent target cell lysis. Moreover, CC-3 induced efficient T cell proliferation and formation of T cell memory subsets. Together, our results emphasize the potential of CC-3, which is presently being GMP-produced to enable clinical evaluation for treatment of pancreatic, hepatic and gastric cancer. Competing Interests: GJ, HS and LZ are listed as inventors on the patent application “Antibodies targeting, and other modulators of, the CD276 antigen, and uses thereof,” EP3822288A1, applicant is German Cancer Research Center, Heidelberg, and Medical Faculty University of Tuebingen, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2023 Lutz, Zekri, Weßling, Berchtold, Heitmann, Lauer, Jung and Salih.)
Databáze:	MEDLINE
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