Epstein-Barr virus (EBV)-based gene delivery vectors that preferentially express toxic genes in EBV-infected cells could be used to target EBV-positive tumors for destruction. We have shown previously that the cytosine deaminase (CD) enzyme, which converts the prodrug 5-fluorocytosine (5-FC) into the toxic compound 5-fluorouracil efficiently kills EBV-positive cells in the presence of 5-FC, with a substantial bystander killing effect in vitro and in vivo. To identify the optimal enzyme/prodrug combination for treating EBV-positive lymphomas, we have compared the effectiveness of the CD/5-FC combination with the nitroreductase (NTR)/CB1954 combination for killing EBV-positive B-cell lines. NTR metabolizes CB1954 into an alkylating agent that cross-links DNA. When the CD gene or the NTR gene were transfected into two different EBV-positive B-cell lines in vitro, approximately 90% of cells were killed in a prodrug-dependent manner, although the transfection efficiency was <5%. However, severe combined immunodeficient mouse tumors containing either 30% or 100% of NTR-expressing Burkitt lymphoma (Jijoye) cells were growth inhibited, but not cured, by treatment with intraperitoneal CB1954 (20 mg/kg/day) for 10 days. These results suggest that the NTR/CB1954 combination induces efficient bystander killing of EBV-positive B-cell lines in vitro but may not be as effective as the CD/5-FC combination for treating B-cell lymphomas in vivo.
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http://dx.doi.org/10.1038/sj.cgt.7700102 | DOI Listing |
Recenti Prog Med
January 2025
Divisione di Ematologia e terapie cellulari, Irccs Ospedale Policlinico San Martino, Genova.
CAR-T therapy (chimeric antigen receptor T-cell) has revolutionized the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) that have relapsed or are refractory to conventional chemotherapies. In particular, patients who have relapsed or are refractory to two lines of therapy are patients who have a poor prognosis. The advent of CAR-T immunotherapy is an innovative approach with which we can give hope of recovery even in the case of refractory disease, even for patients who are not candidates for high-dose therapies, for example due to age.
View Article and Find Full Text PDFMediterr J Hematol Infect Dis
January 2025
Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Italy.
Background: Clonal mature B-cell lymphoproliferative disorders (B-LPDs) are a heterogeneous group of neoplasia characterized by the proliferation of mature B lymphocytes in the peripheral blood, bone marrow and/or lymphoid tissues. B-LPDs classification into different subtypes and their diagnosis is based on a multiparametric approach. However, accurate diagnosis may be challenging, especially in cases of ambiguous interpretation.
View Article and Find Full Text PDFMol Cell Biochem
January 2025
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
The prognosis of B cell acute lymphoblastic leukemia (B-ALL) is poor, primarily due to drug resistance and relapse. Ga15, encoded by GNA15, belongs to the G protein family, with G protein-coupled receptors playing a crucial role in multiple biological process. GNA15 has been reported to be involved in various malignancies; however, its potential role in B-ALL remain unknown.
View Article and Find Full Text PDFNephrol Dial Transplant
January 2025
Division of Nephrology and Hypertension, Rochester, MN, USA.
Background And Hypothesis: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B-cell maturation antigen (BCMA), and chimeric antigen receptor T-cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy.
View Article and Find Full Text PDFMol Ther
January 2025
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School; 30625 Hannover, NI, Germany. Electronic address:
Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B-cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.
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