4 results
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2. Sensitivity Analysis of Mathematical Model to Study the Effect of T Cells Infusion in Treatment of CLL.
- Author
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Anjum, Asad Ur Rehman, Chaudhry, Qasim Ali, and Almatroud, A. Othman
- Subjects
- *
SENSITIVITY analysis , *T cells , *MATHEMATICAL models , *MATHEMATICAL analysis , *CHRONIC lymphocytic leukemia - Abstract
In this paper, we considered a mathematical model concerned with the treatment of Chronic Lymphocytic Leukemia (CLL) taking into account the effect of superficially infused T cells in this particular type of tumor. The model is described thoroughly by the system of non-linear differential equations explaining the interaction of naïve, infected, cancer and immune cell population. The detailed sensitivity analysis with the application is the major part of this paper. The basic objective is to provide insight to how parameters' behavior varies model results by elaborating the results obtained from the application of sensitivity analysis. The sensitivity of the model was evaluated not only theoretically, but also with the help of a numerical approach, producing graphs providing better imminent of results. We argue that the application of the sensitivity analysis method endows an insight into how and which parameters are of primary significance in controlling the spread of leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
3. Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia.
- Author
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Koehler, Philipp, Schmidt, Patrick, Hombach, Andreas A., Hallek, Michael, and Abken, Hinrich
- Subjects
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T cells , *CHRONIC lymphocytic leukemia , *B cells , *CANCER relapse , *CLINICAL trials , *CHIMERIC proteins , *ANTIGEN receptors , *MAJOR histocompatibility complex , *CD19 antigen - Abstract
B-cell chronic lymphocytic leukaemia (B-CLL) remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR) which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
4. B- AND T-LYMPHOCYTE MARKERS ON TRANSFORMED LYMPHOCYTES FROM MITOGEN-STIMULATED CULTURES OF NORMAL AND CLL LYMPHOCYTES AND ON TONSIL BLASTS.
- Author
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Smith, J. L. and Haegert, D.
- Subjects
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T cells , *B cells , *LYMPHOCYTES , *MITOGENS , *CHRONIC lymphocytic leukemia , *IMMUNOGLOBULIN G - Abstract
Mitogen-transformed human peripheral blood lymphocytes and tonsil blasts were examined by rosette formation to detect the presence of membrane-bound immunoglobulin (Ig) and surface receptors for fixed IgG and fixed C3. In addition, the capacity of these cells to rosette with sheep erythrocytes was evaluated as a reaction characteristic of T lymphocytes. In order for clear morphological recognition of the rosetting transformed lymphocytes and the rosetting tonsil blasts a cytocentrifuge technique was developed and used in conjunction with autoradiography and/or with Romanowsky stains. Using these techniques and the culture methods described in this paper phytohaemagglutinin, pokeweed mitogen, streptococcal filtrates and purified protein derivative stimulated predominantly T cells in the peripheral blood of man. A minority of the transformed cells in these mitogen-stimulated cultures (<24%) did rosette with B lymphocyte markers and presumably represent a B-cell response. No significant differences were found between the T- or B-cell specificity of the mitogens investigated. Lymphoid preparations from tonsils excised from normal donors with recurrent tonsillitis were found to contain 6-15% lymphoblasts and the iarge majority of these cells formed rosettes with the B-cell markers, less than 20% of these lymphoblasts formed spontaneous sheep erythrocyte rosettes. Using a mixed rosetting technique a small proportion (<5%) of PHA-transformed cells and tonsil lymphoblasts were found to have combined sheep Fc or combined sheep C3 receptors. The investigation of B- and T-lymphocyte surface markers on mitogentransformed lymphocytes was extended to neopiastic lymphocyte populations and it was found that the majority of transformed cells (>70%) present in chronic lymphocytic leukaemia cultures stimulated with PHA after 6 days incubation were transformed T lymphocytes. [ABSTRACT FROM AUTHOR]
- Published
- 1974
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