The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia
Abstract
Chronic lymphocytic leukemia (CLL) cells can be made to express recombinant CD40-ligand (CD154) by transduction with a replication-defective adenovirus vector (Ad-CD154). Ad-CD154–transduced and bystander leukemia cells become highly effective antigen-presenting cells that can induce CLL-specific autologous cytotoxic T lymphocytes in vitro. This study investigated the immunologic and clinical responses to infusion of autologous Ad-CD154-CLL cells in patients with CLL. After a one-time bolus infusion of autologous Ad-CD154–transduced leukemia cells, there was increased or de novo expression of immune accessory molecules on bystander, noninfected CLL cells in vivo. Treated patients also developed high plasma levels of interleukin-12 and interferon-γ, the magnitudes of which corresponded to absolute blood CD4+T-cell counts before therapy. On average, patients experienced a greater than 240% increase in absolute blood T-cell counts within 1 to 4 weeks of treatment. Moreover, treatment increased the numbers of leukemia-specific T cells, demonstrated by autologous ELISPOT assay and mixed lymphocyte reactions. These biologic effects were associated with reductions in leukemia cell counts and lymph node size. Treatment did not induce autoimmune thrombocytopenia or hemolytic anemia and no dose-limiting toxicity was observed. This approach may provide a novel and effective form of gene therapy for patients with this disease.
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CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help
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Cited by
Molecular mechanism and function of CD40/CD40L engagement in the immune system
Elgueta, R., Benson, M. J., De Vries, V. C., Wasiuk, A., Guo, Y., & Noelle, R. J. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00782.x · Cited by 1,625
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Haematological malignancies: at the forefront of immunotherapeutic innovation
Bachireddy, P., Burkhardt, U. E., Rajasagi, M., & Wu, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3907 · Cited by 85
Metadata
- Authors
- Wierda, W. G., Cantwell, M. J., Woods, S. J., Rassenti, L. Z., Prussak, C. E., & Kipps, T. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-11-01
- Volume
- 96
- Issue
- 9
- Pages
- 2917-2924
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W899734449
- Cited by
- 340
- References
- 22
- FWCI
- 16.41
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wierda, W. G., Cantwell, M. J., Woods, S. J., Rassenti, L. Z., Prussak, C. E., & Kipps, T. J. (2000). CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood. https://doi.org/10.1182/blood.v96.9.2917
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