{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:20:06Z","timestamp":1771104006631,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Jos\u00e9 Carreras Leuk\u00e4mie-Stiftung","award":["DJCLS 12 R\/2021"],"award-info":[{"award-number":["DJCLS 12 R\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytomegalovirus (CMV) reactivation after stem cell or solid organ transplantation remains a major cause of morbidity and mortality in this setting. T-cell receptor (TCR)-like antibodies bind to intracellular peptides presented in major histocompatibility complex (MHC) molecules on the cell surface and may have the potential to replace T-cell function in immunocompromised patients. Three previously selected CMV-specific, human leukocyte antigen (HLA)-restricted (HLA-A*0101, HLA-A*0201 and HLA-B*0702) Fab-antibodies (A6, C1 and C7) were produced as IgG antibodies with Fc optimization. All antibodies showed specific binding to CMV peptide-loaded tumor cell lines and primary fibroblasts expressing the corresponding MHC-I molecules, leading to specific target cell lysis after the addition of natural killer (NK) cells. When deployed in combination as an antibody pool against target cells expressing more than one matching HLA allele, cytotoxic effects were amplified accordingly. CMV-specific TCR-like antibodies were also able to mediate their cytotoxic effects through neutrophils, which is important considering the delayed recovery of NK cells after stem cell transplantation. When tested on patient blood obtained during CMV reactivation, CMV-specific antibodies were able to bind to and induce cytotoxic effects in lymphocytes. CMV-specific TCR-like antibodies may find application in patients with CMV reactivation or at risk of CMV reactivation. In contrast to previous HLA\/peptide-directed therapeutic approaches, the concept of a TCR-like antibody repertoire covering more than one HLA allele would make this therapeutic format available to a much larger group of patients.<\/jats:p>","DOI":"10.3390\/ijms252312908","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"12908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytomegalovirus-Specific T-Cell-Receptor-like Antibodies Target In Vivo-Infected Human Leukocytes Inducing Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-6895","authenticated-orcid":false,"given":"Moritz","family":"Bewarder","sequence":"first","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Christofyllakis","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Petersen","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-3140","authenticated-orcid":false,"given":"Gerhard","family":"Held","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Westpfalz-Klinikum Kaiserslautern, 67655 Kaiserslautern, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3289-6545","authenticated-orcid":false,"given":"Sigrun","family":"Smola","sequence":"additional","affiliation":[{"name":"Institute of Virology, Saarland University Medical Center, 66421 Homburg, Germany"},{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarland University Campus, 66123 Saarbrucken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabi","family":"Carbon","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Bette","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Link","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Kiefer","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-8315","authenticated-orcid":false,"given":"Joerg Thomas","family":"Bittenbring","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Age","family":"Kos","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadim","family":"Lesan","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic","family":"Kaddu-Mulindwa","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Thurner","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-0421","authenticated-orcid":false,"given":"Frank","family":"Neumann","sequence":"additional","affiliation":[{"name":"Internal Medicine I, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Forte, E., Zhang, Z., Thorp, E.B., and Hummel, M. 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