ArticleCancer immunology, immunotherapy : CII2021
Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.The Lancet. Oncology · 2024Trial
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- From monoclonal to polyfunctional immunotherapy: Reprogramming CAR-T-cell therapy with oncolytic viruses in B-cell malignancies.HemaSphere · 2026Article
- Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.Clinical and translational medicine · 2026Review
- Therapeutic potential of oncolytic viruses in hematopoietic malignancies: from preclinical insights to clinical realities.Frontiers in microbiology · 2026Review
- Review
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Oncolytic viruses as cancer therapeutics: From mechanistic insights to clinical translation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Reshaping CAR-T cells through overexpression of T cell factor 1.Frontiers in immunology · 2025Article
- LOAd703 and chemotherapy combination in pancreatic cancer: insights from the LOKON001 study.Translational gastroenterology and hepatology · 2025Article
- Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment.Oncology research · 2025Review
- Measles Virus-Based Genetic Modifications: Progress in Hematological Malignancy Treatment.OncoTargets and therapy · 2025Review
- Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.International journal of molecular sciences · 2024Review
- Emerging roles of intratumor microbiota in cancer: tumorigenesis and management strategies.Journal of translational medicine · 2024Review
- Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.Cancer communications (London, England) · 2024Review
- Alliance between titans: combination strategies of CAR-T cell therapy and oncolytic virus for the treatment of hematological malignancies.Annals of hematology · 2024Review
- CD40 stimulation via CD40 ligand enhances adenovirus-mediated tumour immunogenicity including 'find-me', 'eat-me', and 'kill-me' signalling.Journal of cellular and molecular medicine · 2024Article
- Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.Biomarker research · 2024Review
- Revolutionizing Cancer Treatment: Unleashing the Power of Combining Oncolytic Viruses with CAR-T Cells.Anti-cancer agents in medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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-γ 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.