ArticleHaematologica2012
The cytotoxicity of anti-CD22 immunotoxin is enhanced by bryostatin 1 in B-cell lymphomas through CD22 upregulation and PKC-βII depletion.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Expanding the frontier of CAR therapy: comparative insights into CAR-T, CAR-NK, CAR-M, and CAR-DC approaches.Annals of hematology · 2025Review
- Anticancer Activity of the Marine-Derived Compound Bryostatin 1: Preclinical and Clinical Evaluation.International journal of molecular sciences · 2025Review
- Bryostatin enhances CD20 CAR-T therapy efficacy against B-cell lymphoma by overcoming trogocytosis-mediated antigen loss.Frontiers in immunology · 2025Article
- Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural basis for antibody recognition of the proximal MUC16 ectodomain.Journal of ovarian research · 2024Article
- Targeting CD22 for B-cell hematologic malignancies.Experimental hematology & oncology · 2023Review
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.Frontiers in oncology · 2023Review
- Trimethylene Methane Dianion Equivalent for the Asymmetric Consecutive Allylation of Aldehydes: Applications to Prins-Driven Macrocyclizations for the Synthesis of Bryostatin 1 and Analogues.The Journal of organic chemistry · 2022Article
- Novel molecules as the emerging trends in cancer treatment: an update.Medical oncology (Northwood, London, England) · 2022Review
- Bryostatin Activates CAR T-Cell Antigen-Non-Specific Killing (CTAK), and CAR-T NK-Like Killing for Pre-B ALL, While Blocking Cytolysis of a Burkitt Lymphoma Cell Line.Frontiers in immunology · 2022Article
- Imagining the cell therapist: Future CAR T cell monitoring and intervention strategies to improve patient outcomes.EJHaem · 2022Review
- Custom CARs: Leveraging the Adaptability of Allogeneic CAR Therapies to Address Current Challenges in Relapsed/Refractory DLBCL.Frontiers in immunology · 2022Review
- CAR-T cell therapy for hematological malignancies: Limitations and optimization strategies.Frontiers in immunology · 2022Review
- Surface expression of the immunotherapeutic target GCancer reports (Hoboken, N.J.) · 2021Article
- Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects.Acta pharmaceutica Sinica. B · 2021Review
- Function-Oriented Synthesis: Design, Synthesis, and Evaluation of Highly Simplified Bryostatin Analogues.The Journal of organic chemistry · 2020Article
- Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes.Marine drugs · 2020Review
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Prodrugs of PKC modulators show enhanced HIV latency reversal and an expanded therapeutic window.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.Nature communications · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn spite of potent first-line therapies for chronic lymphocytic leukemia, treatment remains palliative and all patients frequently relapse. Treatment options for these patients are more limited. BL22 is a recombinant protein composed of the variable region of a monoclonal antibody that binds to CD22 and of PE38, a truncated Pseudomonas exotoxin. BL22 is a very potent drug already used in patients with hairy cell leukemia, whereas in chronic lymphocytic leukemia its cytotoxicity is limited by a lower expression of CD22. Here we demonstrate that this limitation can be overcome by pre-activation of chronic lymphocytic leukemia cells with bryostatin 1. DESIGN AND
methodsPrimary malignant B cells from chronic lymphocytic leukemia and mantle cell lymphoma patients were used in vitro to assess the therapeutic impact of drug combinations using BL22 and bryostatin 1.
resultsWe demonstrate that bryostatin 1 sensitizes chronic lymphocytic leukemia cells for the cytotoxic effects of BL22 through activation of protein kinase C and subsequently increased CD22 surface expression. Dose and time response analysis reveals that activation of protein kinase C further activates an autocrine feedback loop degrading protein kinase C-βII protein. Depletion of protein kinase C-βII and upregulation of CD22 persist for several days following pre-stimulation with bryostatin 1. Therefore, our data provide a rationale for the sequential administration of BL22 following bryostatin 1 treatment. In addition to primary chronic lymphocytic leukemia cells, bryostatin 1 also sensitizes diffuse large B-cell lymphoma and mantle cell lymphoma cells to BL22 induced apoptosis.
conclusionsOur data suggest that the combination of bryostatin 1 with antibodies directed against CD22 is a potent drug combination for the treatment of low- and high-grade 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.