{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["33(4)"],"submitter":["Renner A"],"pubmed_abstract":["Despite the success of cell therapy in treating hematological malignancies, the treatment of solid tumors remains challenging due to the tumor microenvironment (TME) and a lack of suitable antigens. To address this, we investigated a putative octapeptide neoepitope generated by proteolytic cleavage of the stress-induced protein MHC class I polypeptide-related sequence B (MICB). Antibodies developed via the hybridoma technique exhibited high affinity and specificity toward the octapeptide. Detection of the octapeptide was enhanced by inserting an α-helical linker before the transmembrane domain, improving accessibility on stably transduced cells. Two chimeric antigen receptor (CAR) constructs with differing single-chain variable fragment (scFv) chain orientations were expressed in primary T and natural killer (NK) cells, showing antigen-specific cytotoxicity, particularly when incorporating the rigid linker. Variations in sensitivity between CARs influenced killing efficacy and activation profiles. Oncolytic measles virus (MV) was used as a vector encoding the membrane-anchored octapeptide, selectively infecting tumor cells and enhancing CAR-T cell-mediated cytotoxicity. Combined use of CAR-T and (CAR-)NK cells demonstrated increased persistence of immune cells as well as potent and sustained antitumor effects following MV infection. This study underscores the potential of neoepitope-based CAR therapy for targeting solid tumor cells and highlights the potential synergistic effects of combining cell therapy with virotherapy for improved therapeutic outcomes."],"journal":["Molecular therapy. Oncology"],"pagination":["201043"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12495166"],"repository":["biostudies-literature"],"pubmed_title":["Enhanced solid tumor cell targeting by a neoepitope-encoding oncolytic measles virus combined with CAR therapy."],"pmcid":["PMC12495166"],"pubmed_authors":["Delaroque N","Engeland CE","Finkbeiner MSC","Haas FV","Koehl U","Stahringer A","Szardenings M","Renner A","Fricke S","Lindow M","Schmiedel D"],"additional_accession":[]},"is_claimable":false,"name":"Enhanced solid tumor cell targeting by a neoepitope-encoding oncolytic measles virus combined with CAR therapy.","description":"Despite the success of cell therapy in treating hematological malignancies, the treatment of solid tumors remains challenging due to the tumor microenvironment (TME) and a lack of suitable antigens. To address this, we investigated a putative octapeptide neoepitope generated by proteolytic cleavage of the stress-induced protein MHC class I polypeptide-related sequence B (MICB). Antibodies developed via the hybridoma technique exhibited high affinity and specificity toward the octapeptide. Detection of the octapeptide was enhanced by inserting an α-helical linker before the transmembrane domain, improving accessibility on stably transduced cells. Two chimeric antigen receptor (CAR) constructs with differing single-chain variable fragment (scFv) chain orientations were expressed in primary T and natural killer (NK) cells, showing antigen-specific cytotoxicity, particularly when incorporating the rigid linker. Variations in sensitivity between CARs influenced killing efficacy and activation profiles. Oncolytic measles virus (MV) was used as a vector encoding the membrane-anchored octapeptide, selectively infecting tumor cells and enhancing CAR-T cell-mediated cytotoxicity. Combined use of CAR-T and (CAR-)NK cells demonstrated increased persistence of immune cells as well as potent and sustained antitumor effects following MV infection. This study underscores the potential of neoepitope-based CAR therapy for targeting solid tumor cells and highlights the potential synergistic effects of combining cell therapy with virotherapy for improved therapeutic outcomes.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-04T05:41:15.09Z","creation":"2026-06-04T03:06:19.793Z"},"accession":"S-EPMC12495166","cross_references":{"pubmed":["41050431"],"doi":["10.1016/j.omton.2025.201043"]}}