T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target.

Autor: Mayer KE; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Mall S; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany., Yusufi N; Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Gosmann D; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Steiger K; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Russelli L; Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Bianchi HO; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Audehm S; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Wagner R; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Bräunlein E; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Stelzl A; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Bassermann F; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany., Weichert W; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Weber W; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Schwaiger M; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., D'Alessandria C; Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Krackhardt AM; Clinic and Policlinic for Internal Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner-site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Theranostics [Theranostics] 2018 Nov 28; Vol. 8 (21), pp. 6070-6087. Date of Electronic Publication: 2018 Nov 28 (Print Publication: 2018).
DOI: 10.7150/thno.27275
Abstrakt: Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer. However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders. Current imaging techniques using 18 F-fluorodeoxyglucose-positron-emmission-tomograpy ( 18 F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation. Therefore, direct imaging of T cells at the tumor site represents a highly attractive tool to evaluate effective tumor rejection or evasion. Moreover, such markers may be suitable for theranostic imaging. Methods: We mainly investigated the potential of two novel pan T-cell markers, CD2 and CD7, for T-cell tracking by immuno-PET imaging. Respective antibody- and F(ab´) 2 fragment-based tracers were produced and characterized, focusing on functional in vitro and in vivo T-cell analyses to exclude any impact of T-cell targeting on cell survival and antitumor efficacy. Results: T cells incubated with anti-CD2 and anti-CD7 F(ab´) 2 showed no major modulation of functionality in vitro , and PET imaging provided a distinct and strong signal at the tumor site using the respective zirconium-89-labeled radiotracers. However, while T-cell tracking by anti-CD7 F(ab´) 2 had no long-term impact on T-cell functionality in vivo , anti-CD2 F(ab´) 2 caused severe T-cell depletion and failure of tumor rejection. Conclusion: This study stresses the importance of extended functional T-cell assays for T-cell tracer development in cancer immunotherapy imaging and proposes CD7 as a highly suitable target for T-cell immuno-PET imaging.
Competing Interests: Competing Interests: M.S. received a commercial research grant from Siemens Medical Research and speakers´ bureau honoraria from Siemens Lunch Symposium, and he has ownership interest (including patents) in Siemens. The other authors have no competing interest to declare.
Databáze: MEDLINE
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