scholarly journals Hodgkin's lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments

2006 ◽  
Vol 60 (10) ◽  
pp. 1092-1097 ◽  
Author(s):  
C. Atayar ◽  
A. van den Berg ◽  
T. Blokzijl ◽  
M. Boot ◽  
R. D Gascoyne ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Transcription Factor Profile

scholarly journals Outcome in Hodgkin's Lymphoma Can Be Predicted from the Presence of Accompanying Cytotoxic and Regulatory T Cells

2005 ◽  
Vol 11 (4) ◽  
pp. 1467-1473 ◽  
Author(s):  
Tomás Álvaro ◽  
Marylène Lejeune ◽  
Ma Teresa Salvadó ◽  
Ramón Bosch ◽  
Juan F. García ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma

Development of Effective Immunotherapy for B-Cell Non-Hodgkin’s Lymphoma with CD19-Specific Cytotoxic T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3277-3277
Author(s):  
Keichiro Mihara ◽  
Kazuyoshi Yanagihara ◽  
Chihaya Imai ◽  
Akiro Kimura ◽  
Dario Campana
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Killing ◽  
Hodgkin's Lymphoma ◽  
Single Chain ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Less than 60% of patients with B-cell non-Hodgkin’s lymphoma (B-NHL) can be cured with contemporary therapy. Using artificial receptors it is possible to redirect the specificity of immune cells to tumor-associated antigens, a strategy that holds great potential as a novel cancer therapy. Since B-NHL cells invariably express CD19, we transduced human peripheral blood T lymphocytes with a recently developed receptor (anti-CD19-BB-ζ), which consists of the single-chain variable domain (scFv) of an anti-CD19 monoclonal antibody, the hinge and transmembrane domains of CD8α, and the signaling domains of CD3ζ and 4-1BB. CD3ζ delivers the primary stimulus upon receptor engagement, while 4-1BB delivers co-stimulatory signals that are crucial for T-cell cytotoxicity. It has been shown that elicitation of 4-1BB signaling enhances the immune response to tumors in vivo, even when an immune response cannot be induced by CD28 stimulation. Retroviral transduction led to anti-CD19-BB-ζ expression in T cells with high efficiency: median percent of transduced cells was 60.3% (range, 25.7%–83.4%; n = 9). T lymphocytes expressing anti-CD19-BB-ζ expanded more vigorously that T cells transduced with receptors lacking 4-1BB and exerted powerful cytotoxicity against the CD19+ B-NHL cell lines Raji, Daudi, RL, and HT in vitro: at a 0.5: 1 effector: target ratio, mean (± SD) cell specific lymphoma cell killing was 96.6% ± 4.6% after 5–7 days of culture (4 experiments in each cell line). Transduced T cells were also effective against freshly isolated cells from patients with diffuse large, follicular large, Burkitt, and mantle cell lymphoma cultured on bone marrow-derived mesenchymal cells: in 10 samples, cell killing was 93.6% ± 5.7% at a 0.5: 1 ratio after 5–7 days of culture. Sensitivity to anti-CD19-BB-ζ-mediated killing was observed regardless of high Bcl-2 expression. T cells expressing anti-CD19-BB-ζ were also effective in a xenograft model of NHL, in which NOD/SCID mice were inoculated subcutaneously with lymphoma cells (1 x 107). Subsequent inoculation of T cells (2 x 106) transduced with anti-CD19-BB-ζ receptors significantly suppressed tumor growth, whereas inoculation of T cells transduced with empty control vector had no effect (3 mice for each treatment). These results provide a rationale for clinical testing of autologous T cells modified with anti-CD19-BB-ζ receptors in patients with aggressive or relapsed B-NHLs refractory to conventional therapy.

Complete Tumor Responses in Lymphoma Patients Who Receive Autologous Cytotoxic T Lymphocytes Targeting EBV Latent Membrane Proteins

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 230-230
Author(s):  
Catherine M. Bollard ◽  
Maja Stanojevic ◽  
Ann M. Leen ◽  
Teresita Lopez ◽  
Andrea N. Sheehan ◽  
...  
Keyword(s):  
T Cells ◽  
Partial Response ◽  
Hodgkin’S Lymphoma ◽  
Flow Cytometric Analysis ◽  
Hodgkin's Lymphoma ◽  
Effector Cells ◽  
Non Hodgkin Lymphoma ◽  
Tumor Associated Antigen ◽  
Clinical Responses ◽  
Non Hodgkins Lymphoma

Abstract EBV-associated Hodgkin’s Lymphoma (HL) and some non-Hodgkins lymphoma (NHL) have type II viral latency expressing the subdominant EBV antigens EBNA1, LMP1 and LMP2. These antigens may serve as targets for immunotherapy approaches and in previous studies, we used polyclonal EBV-specific CTL in patients with relapsed EBV +ve HL obtaining 2 complete and 1 partial response in 11 patients. Analyses of EBV-CTL lines showed that small populations of T cells reactive against the tumor-associated antigen LMP2 were present in the majority of the infused lines, with some expansion in the peripheral blood following infusion. We therefore hypothesized that CTL enriched for effector cells specifically targeting LMP antigens would have greater efficacy in these patients. LMP-CTL were generated using dendritic cells for initial stimulations then EBV-transformed lymphoblastoid cell lines (LCL) both of which had been genetically modified to overexpress either LMP2 alone or inactive LMP1 (ΔLMP1) and LMP2 by transduction with an Ad5f35LMP2 (n=16) or Ad5f35ΔLMP1-I-LMP2 (n=14) vector respectively. All LMP-CTL lines were polyclonal comprising CD4+ (mean 17±18%; range 1–92%) and CD8+ (mean 74 ± 25%; range 1–99%) T-cells. Flow cytometric analysis of memory markers revealed mixed populations of CD45RA- CD62L- T-cells (45±15%; range 31–63%) and CD45RA- CD62L+ T-cells (34±5%; range 28–41%). The CTL lines had specificity for CD4+ and CD8+ restricted LMP2 epitopes alone (n=19; mean 1; range 0–7) or both LMP1 and LMP2 epitopes (n=13; mean 2; range 0–6) per CTL line, as determined using overlapping LMP1 and LMP2 peptide pools in ELISPOT assays. Twenty-four patients with EBV+ Hodgkin’s Lymphoma and non-Hodgkin Lymphoma have been treated on dose escalation studies. 16 with LMP2 CTLs and 8 with LMP1/2 CTLs. No immediate toxicity was observed. After CTL infusion, increased numbers of LMP-specific T cells were detected in the blood of 15/22 evaluable patients, (range 2 to 70 fold) persisting for up to 3 months. Additionally, two patients had lymph node biopsies 3–6 months post CTL, which showed selective accumulation of LMP2-multimer positive cells in lymph nodes. 12/13 high-risk and/or multiply relapsed patients who received LMP-CTL as adjuvant treatment after chemotherapy remain in remission for a median of 2years (range >3months to >5years) after CTL. 11 patients had detectable disease at the time of CTL, 2 of these had progressive disease by 8 weeks and 9 had clinical responses. The median duration of the clinical responses is 1 year with one stable disease (>12months), one partial response (36 months) and 7 complete responses (range 9 months to >4.5 years). One of the complete responders was biopsied 7 weeks after receiving CTL, which were predominantly CD4+ (92%). Increased CD4+ T cells were seen compared to pre-CTL biopsy specimens and imaging studies confirmed remission. In conclusion, immunotherapy with CTL targeting LMP antigens is well tolerated in patients with EBV+ lymphoma and infused LMP-CTL can accumulate at tumor sites and induce complete and sustained clinical responses.

T-bet, a T cell–associated transcription factor, is expressed in Hodgkin's lymphoma

2005 ◽  
Vol 36 (1) ◽  
pp. 10-15 ◽  
Author(s):  
David M. Dorfman ◽  
Eun Sook Hwang ◽  
Aliakbar Shahsafaei ◽  
Laurie H. Glimcher
Keyword(s):  
Transcription Factor ◽  
T Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma

Immunoregulatory T Cells in the Peripheral Blood of Patients with Hodgkin’s Lymphoma

2006 ◽  
Vol 116 (3) ◽  
pp. 181-185 ◽  
Author(s):  
Sándor Baráth ◽  
Magdolna Aleksza ◽  
Katalin Keresztes ◽  
Judit Tóth ◽  
Sándor Sipka ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Immunoregulatory T Cells
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