In vivo proliferation characteristics of reactive T-lymphocytes in B-cell non-Hodgkin's lymphoma (NHL), G. Goverde, J. Raemaekers, A. Pennings, J. Bogman, J. Boezeman, H. Wessels, T. de Witte.

1996 ◽  
Vol 48 (5) ◽  
pp. A56-A57
Keyword(s):  
T Lymphocytes ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non 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.

scholarly journals T lymphocytes from invaded lymph nodes in patients with B-cell-derived non-Hodgkin's lymphoma: reactivity toward the malignant clone

Blood ◽  
1990 ◽  
Vol 75 (5) ◽  
pp. 1154-1162 ◽  
Author(s):  
MC Jacob ◽  
MP Piccinni ◽  
T Bonnefoix ◽  
MF Sotto ◽  
P Couderc ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lymph Nodes ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Interleukin 2 ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Group 12 ◽  
Non Hodgkin's Lymphoma

Tumor-infiltrating T lymphocytes (TIL-T) are always present in B-cell- derived non-Hodgkin's lymphoma (NHL). In this investigation, we explored the possibility that collaboration might exist between these cells. TIL-T were isolated from 39 lymph nodes of patients with NHL. In most of the cases, few of them (less than 10%) possessed surface activation receptors CD25 or OKT9. In 80% of the cases, they proliferated in response to recombinant interleukin-2 (rIL-2), but the degree of proliferation was often low as compared with control populations. The influence of irradiated autologous malignant cells on the TIL-T proliferation in response to rIL-2 (40 U/mL) was also investigated: in 38% of the cases, this proliferation was not modified (group O), and in 41% it was higher (group +) and in 21% it was lower (group -). The mechanism of this immune response (specific or not) is not elucidated at present. The definition of these groups was statistically correlated with different parameters of the disease: (1) percentage of TIL-T was higher in group + (44% +/- 17%) than in group O (31% +/- 18%) and group - (24% +/- 15%); (2) B-cell proliferation in centrofollicular lymphomas was more frequently nodular or nodular and diffuse in group + (83%) and O (55%) than in group - (0%); (3) low- grade malignancies in the Working Formulation were more frequent in group + (75%) than in group O (60%) or group - (12%); (4) favorable prognosis evaluated with the Grenoble cytologic classification was more frequent in group + and O (87%) than in group - (12%); (5) actuarial survival curves showed a significantly better prognosis for patients in group +.

scholarly journals Functional expression of adhesion receptors and costimulatory molecules by fresh and immortalized B-cell non-Hodgkin's lymphoma cells

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2802-2812 ◽  
Author(s):  
FA Vyth-Dreese ◽  
TA Dellemijn ◽  
JW van Oostveen ◽  
CA Feltkamp ◽  
A Hekman
Keyword(s):  
T Lymphocytes ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Non Hodgkin’S Lymphoma ◽  
Hla Dr ◽  
Non Hodgkin's Lymphoma ◽  
Accessory Molecules

Peripheral blood lymphocytes of a patient with follicular B-cell non- Hodgkin's lymphoma (B-NHL) were immortalized in vitro by Epstein-Barr virus (EBV). Eight cell lines were obtained (termed BNS1, BNS2–1 through BNS2–7), which showed a pattern of idiotypic (id) Ig surface expression and Ig JH and kappa gene rearrangement, identical to that of the parent cells (termed NS), confirming their neoplastic origin. Induction of allogeneic T-cell proliferation by NS cells was mediated by HLA-DR, leukocyte function-associated antigen-1 (LFA-1), LFA-3, B7–1/CD80, and CTLA4 and resulted in the upregulation (LFA-3, intercellular adhesion molecule-1 [ICAM-1], CD40) and induction (B7–1/CD80, B7–2/CD86, L16/activated LFA-1) of accessory molecules on NS cells. In turn, responder T lymphocytes were induced to express B7–1/CD80, B7–2/CD86, CD40 ligand (CD40L), ICAM-1, L16/activated LFA-1, and HLA-DR, reflecting bidirectional signaling between T lymphocytes and B-NHL cells. Preactivation of NS cells by EBV transformation or CD40 engagement resulted in enhanced expression of accessory molecules and abolished the requirement for accessory cells during allostimulation. These resting and activated clonal B cells will be useful in further dissecting the requirements for B-NHL costimulation.

scholarly journals T lymphocytes from invaded lymph nodes in patients with B-cell-derived non-Hodgkin's lymphoma: reactivity toward the malignant clone

Blood ◽  
1990 ◽  
Vol 75 (5) ◽  
pp. 1154-1162 ◽  
Author(s):  
MC Jacob ◽  
MP Piccinni ◽  
T Bonnefoix ◽  
MF Sotto ◽  
P Couderc ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lymph Nodes ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Interleukin 2 ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Group 12 ◽  
Non Hodgkin's Lymphoma

Abstract Tumor-infiltrating T lymphocytes (TIL-T) are always present in B-cell- derived non-Hodgkin's lymphoma (NHL). In this investigation, we explored the possibility that collaboration might exist between these cells. TIL-T were isolated from 39 lymph nodes of patients with NHL. In most of the cases, few of them (less than 10%) possessed surface activation receptors CD25 or OKT9. In 80% of the cases, they proliferated in response to recombinant interleukin-2 (rIL-2), but the degree of proliferation was often low as compared with control populations. The influence of irradiated autologous malignant cells on the TIL-T proliferation in response to rIL-2 (40 U/mL) was also investigated: in 38% of the cases, this proliferation was not modified (group O), and in 41% it was higher (group +) and in 21% it was lower (group -). The mechanism of this immune response (specific or not) is not elucidated at present. The definition of these groups was statistically correlated with different parameters of the disease: (1) percentage of TIL-T was higher in group + (44% +/- 17%) than in group O (31% +/- 18%) and group - (24% +/- 15%); (2) B-cell proliferation in centrofollicular lymphomas was more frequently nodular or nodular and diffuse in group + (83%) and O (55%) than in group - (0%); (3) low- grade malignancies in the Working Formulation were more frequent in group + (75%) than in group O (60%) or group - (12%); (4) favorable prognosis evaluated with the Grenoble cytologic classification was more frequent in group + and O (87%) than in group - (12%); (5) actuarial survival curves showed a significantly better prognosis for patients in group +.

The Expression of the CD21 Antigen in Non-Hodgkin’s Lymphoma Is Involved in LFA-1 Expression and Tumor Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2285-2285 ◽  
Author(s):  
Masaki Otsuka ◽  
Yoshihiro Yakushijin ◽  
Makoto Hamada ◽  
Takaaki Hato ◽  
Masaki Yasukawa ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Aggregation ◽  
Hodgkin's Lymphoma ◽  
Confocal Laser ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Tumor Survival

Abstract CD21/complement receptor type 2 is a membrane protein expressed on B lymphocytes, follicular dendritic cells, early thymocytes, and a subset of mature T lymphocytes. This major B cell antigen appears later than CD19 and CD20 in cell differentiation and is lost from the cell surface during the early stages of B cell activation. CD21 is characterized not only as a complement ligand but also as an adhesion molecule of the cell surface that is dependent on CD23 expression, suggesting that it may be involved in lymphocyte trafficking and several immune responses. Recently two groups have reported that CD21 expression is significantly negatively associated with mortality in diffuse large B cell lymphomas. From these reports and clinical observations, we have transfected the CD21 gene into a CD21/CD23-negative lymphoma cell line (Namalwa). Interestingly, all established CD21+ transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culturing, and none of the anti-CD21 antibodies prevented this cell aggregation. Moreover, these CD21+ transfectants were easily rejected in vivo when they were injected in nude mice compared to vector-only transfectants and parental cells as controls. These observations suggest that other adhesion molecules may be involved in CD21-induced cell aggregation and reduced tumorgenesis in vivo. After the screening of several integrins, CD21+ transfectants highly expressed LFA-1 (CD11a/CD18) on their cell surfaces compared to vector-only transfectants and parental cells. CD21+ transfectants displayed tight adhesion when in contact with recombinant human ICAM-1, and cell aggregation of CD21+ transfectants was blocked by an anti-LFA-1 monoclonal antibody. Northern and Western analysis and confocal laser scanning microscopic analysis suggested that the CD21 expression made the transfer of LFA-1 from the cytoplasm to the cell surface. We conclude that the expression of the CD21 molecule is strongly associated with the LFA-1 expression on the cell surface, independent of the CD23 molecule, and this phenomenon may be involved in tumor survival in non-Hodgkin’s lymphoma in vivo.

CD45RA expression by CD4 T lymphocytes in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)

1992 ◽  
Vol 39 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Marie-Christine Jacob ◽  
Mireille Favre ◽  
FrançOis Lemarc'Hadour ◽  
Marie-France Sotto ◽  
Thierry Bonnefoix ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin’S Disease ◽  
Hodgkin's Lymphoma ◽  
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.

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