T cells recognize the VH complementarity-determining region 3 of the idiotypic protein of B cell non-Hodgkin's lymphoma

1997 ◽  
Vol 27 (4) ◽  
pp. 1043-1047 ◽  
Author(s):  
Yue-Jin Wen ◽  
Seah H. Lim
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Complementarity Determining Region

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.

Peripheral T cells of patients with B cell non-Hodgkin's lymphoma show a shift in their memory status

2005 ◽  
Vol 29 (9) ◽  
pp. 1019-1027 ◽  
Author(s):  
Djordje Atanackovic ◽  
Jens Panse ◽  
Philippe Schafhausen ◽  
Christiane Faltz ◽  
Katrin Bartels ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Peripheral T Cells ◽  
Memory Status

scholarly journals Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin’s Lymphoma

2019 ◽  
Vol 15 ◽  
pp. 60-68 ◽  
Author(s):  
Zhitao Ying ◽  
Ting He ◽  
Xiaopei Wang ◽  
Wen Zheng ◽  
Ningjing Lin ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Car T Cells ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Car T

scholarly journals Malignant B Cells Skew the Balance of Regulatory T Cells and TH17 Cells in B-Cell Non-Hodgkin's Lymphoma

2009 ◽  
Vol 69 (13) ◽  
pp. 5522-5530 ◽  
Author(s):  
Zhi-Zhang Yang ◽  
Anne J. Novak ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
Stephen M. Ansell
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Th17 Cells ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

scholarly journals TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin’s lymphoma

Leukemia ◽  
2014 ◽  
Vol 28 (9) ◽  
pp. 1872-1884 ◽  
Author(s):  
Z-Z Yang ◽  
D M Grote ◽  
B Xiu ◽  
S C Ziesmer ◽  
T L Price-Troska ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Memory T Cells ◽  
Hodgkin's Lymphoma ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

scholarly journals Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma

2021 ◽  
Vol 9 (2) ◽  
pp. e002097
Author(s):  
Kathryn Lurain ◽  
Ramya Ramaswami ◽  
Ralph Mangusan ◽  
Anaida Widell ◽  
Irene Ekwede ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hiv And Aids ◽  
Hodgkin's Lymphoma ◽  
People Living With Hiv ◽  
Oncogenic Viruses ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

BackgroundNon-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

scholarly journals Prognostic significance of bcl-2 protein expression in aggressive non- Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Independent Effect ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

Sign in / Sign up

Export Citation Format

Share Document