{"entity": "publication", "iuid": "36f6a94e878544f0a557387b3309e12b", "timestamp": "2026-09-01T08:28:38.134Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/36f6a94e878544f0a557387b3309e12b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/36f6a94e878544f0a557387b3309e12b"}}, "title": "Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy.", "authors": [{"family": "Wenthe", "given": "Jessica", "initials": "J", "orcid": "0000-0003-4385-7568", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bc4cbbff70a944af8f477c2a78f79c98.json"}}, {"family": "Naseri", "given": "Sedigheh", "initials": "S"}, {"family": "Labani-Motlagh", "given": "Alireza", "initials": "A"}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}, {"family": "Wikstr\u00f6m", "given": "Kristina I", "initials": "KI"}, {"family": "Eriksson", "given": "Emma", "initials": "E"}, {"family": "Loskog", "given": "Angelica", "initials": "A"}, {"family": "L\u00f6vgren", "given": "Tanja", "initials": "T"}], "type": "journal article", "published": "2021-10-00", "journal": {"title": "Cancer Immunol. Immunother.", "issn": "1432-0851", "volume": "70", "issue": "10", "pages": "2851-2865", "issn-l": "0340-7004"}, "abstract": "Pretreatment of B-cell lymphoma patients with immunostimulatory gene therapy using armed oncolytic viruses may prime tumor lesions for subsequent chimeric antigen receptor (CAR) T-cell therapy, thereby enhancing CAR T-cell functionality and possibly increasing response rates in patients. LOAd703 (delolimogene mupadenorepvec) is an oncolytic adenovirus (serotype 5/35) that encodes for the transgenes CD40L and 4-1BBL, which activate both antigen-presenting cells and T cells. Many adenoviruses failed to demonstrate efficacy in B-cell malignancies, but LOAd703 infect cells via CD46, which enables B cell infection. Herein, we investigated the therapeutic potential of LOAd703 in human B-cell lymphoma models, alone or in combination with CAR T-cell therapy. LOAd703 could infect and replicate in B-cell lymphoma cell lines (BC-3, Karpas422, Daudi, DG-75, U-698) and induced an overall enhanced immunogenic profile with upregulation of co-stimulatory molecules CD80, CD86, CD70, MHC molecules, death receptor Fas and adhesion molecule ICAM-1. Further, CAR T-cell functionality was boosted by stimulation with lymphoma cells infected with LOAd703. This was demonstrated by an augmented release of IFN-\u03b3 and granzyme B, increased expression of the degranulation marker CD107a, fewer PD-1 + TIM-3+ CAR T cells in vitro and enhanced lymphoma cell killing both in in vitro and in vivo xenograft models. In addition, LOAd703-infected lymphoma cells upregulated the secretion of several chemokines (CXCL10, CCL17, CCL22, CCL3, CCL4) essential for immune cell homing, leading to enhanced CAR T-cell migration. In conclusion, immunostimulatory LOAd703 therapy is an intriguing approach to induce anti-lymphoma immune responses and to improve CAR T-cell therapy in B-cell lymphoma.", "doi": "10.1007/s00262-021-02895-7", "pmid": "33666760", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8423656"}, {"db": "pii", "key": "10.1007/s00262-021-02895-7"}], "notes": [], "created": "2026-08-21T11:06:23.147Z", "modified": "2026-08-21T11:06:23.197Z"}