ArticleHaematologica2021
CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
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- Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.Journal of translational medicine · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- The future directions of CAR-T Cell therapy: unlocking the potential of immunotherapy in cancer treatment.Frontiers in molecular medicine · 2026Review
- Comparative analysis of second and third-generation nanobody-based CAR-NK cells targeting PSMA in prostate cancer immunotherapy:Iranian journal of basic medical sciences · 2026Article
- Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.Frontiers in immunology · 2026Review
- Article
- Innovative approaches to CAR-T cell therapy: the role of lipid metabolism pathways.Journal of translational medicine · 2025Review
- EZH1/EZH2 inhibition enhances adoptive T cell immunotherapy against multiple cancer models.Cancer cell · 2025Article
- European survey on CAR T-Cell analytical methods from apheresis to post-infusion immunomonitoring.Frontiers in immunology · 2025Article
- Current landscape of CAR-therapy for osteosarcoma and rhabdomyosarcoma.Frontiers in immunology · 2025Review
- Advances in CAR optimization strategies based on CD28.Frontiers in immunology · 2025Review
- Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells.Journal of hematology & oncology · 2024Article
- Functional Activity of Cytokine-Induced Killer Cells Enhanced by CAR-CD19 Modification or by Soluble Bispecific Antibody Blinatumomab.Antibodies (Basel, Switzerland) · 2024Article
- GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?Frontiers in immunology · 2024Review
- Treatment of multiple myeloma: What is the impact on T-cell function?Therapeutic advances in hematology · 2024Review
- CRISPR/Cas9 system: recent applications in immuno-oncology and cancer immunotherapy.Experimental hematology & oncology · 2023Review
- Deciphering the genetic basis of immune thrombocytopenia: current evidence for genetic predisposition in adult ITP.Blood advances · 2023Review
Corrections and comments
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Authors and funding
30 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prognosis of many patients with chemotherapy-refractory or multiply relapsed CD30+ non-Hodgkin Lymphoma (NHL) or Hodgkin lymphoma (HL) still remains poor, and novel therapeutic approaches are warranted to address this unmet clinical need. In light of this consideration, we designed and pre-clinically validated a Chimeric Antigen Receptor (CAR) construct characterized by a novel anti-CD30 single-chain variable-fragment cassette, linked to CD3ζ by the signaling domains of two costimulatory molecules, namely either CD28.4-1BB or CD28.OX40. We found that CAR.CD30 T-cells exhibit remarkable cytolytic activity in vitro against HL and NHL cell lines, with sustained proliferation and pro-inflammatory cytokine production, even after multiple and sequential lymphoma cell challenges. CAR.CD30 T-cells also demonstrated anti-lymphoma activity in two in vivo xenograft immune-deficient mouse models of metastatic HL and NHL. We observed that administration of CAR.CD30 T-cells, incorporating the CD28.OX40 costimulatory domains and manufactured in the presence of IL7 and IL15, were associated with the best overall survival in the treated mice, along with the establishment of a long-term immunological memory, able to protect mice from further tumor re-challenge. Our data indicate that, in the context of in vivo systemic metastatic xenograft mouse models, the costimulatory machinery of CD28.OX40 is crucial for improving persistence, in vivo expansion and proliferation of CAR.CD30 T-cells upon tumor encounter. CD28.OX40 costimulatory combination is ultimately responsible for the antitumor efficacy of the approach, paving the way to translate this therapeutic strategy in patients with CD30+ HL and NHL.
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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.