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 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 +.

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.

Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up

2004 ◽  
Vol 22 (23) ◽  
pp. 4711-4716 ◽  
Author(s):  
Myron S. Czuczman ◽  
Robin Weaver ◽  
Baha Alkuzweny ◽  
Judy Berlfein ◽  
Antonio J. Grillo-López
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Molecular Remission ◽  
Prior Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Long-term follow-up with updated time to disease progression (TTP) and duration of response (DR) data are presented from a multicenter, phase II trial of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma (NHL). Revised response rates based on International Workshop Response Criteria are also provided. Patients and Methods Enrollment began in April 1994 and consisted of patients with histologically confirmed, low-grade, B-cell lymphoma who had received no prior chemotherapy or who had no more than four prior standard therapies. Patients received six cycles of CHOP and six infusions of rituximab. Results Eight (21%) of the 38 treated patients were classified as International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior chemotherapy. Nine (24%) of 38 were considered poor risk according to the Follicular Lymphoma International Prognostic Index. Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. Conclusion Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.

The use of interleukin-2 and lymphokine-activated killer cells for the treatment of patients with non-Hodgkin's lymphoma.

1992 ◽  
Vol 10 (1) ◽  
pp. 33-40 ◽  
Author(s):  
J S Weber ◽  
J C Yang ◽  
S L Topalian ◽  
D J Schwartzentruber ◽  
D E White ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Low Grade ◽  
Phase Ii Trials ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE The study was undertaken to assess whether immunotherapy regimens with bolus high-dose interleukin-2 (IL-2) alone or with lymphokine-activated killer (LAK) cells are active in previously treated, relapsed patients with non-Hodgkin's lymphoma. PATIENTS AND METHODS Nineteen patients with low- or intermediate-grade lymphomas were treated with bolus high-dose IL-2 alone (11 patients) or IL-2 with LAK cells (eight patients). IL-2 was administered by intravenous bolus infusion at 720,000 IU/kg every 8 hours. Eight patients had low-grade histologies; 11 patients were intermediate-grade. Eighteen patients had received second- or third-generation combination chemotherapy, and eight had also received radiation. All 19 relapsed after a median of two chemotherapy regimens. RESULTS Four responses were observed, three partial and one complete, in patients with follicular histologies who received IL-2 with LAK cells. Response durations were 10, 16, 16, and 26 months, and three responders were re-treated after relapse with subsequent disease control for an additional 16, 39+, and 2+ months, respectively. CONCLUSION High-dose, bolus IL-2-based immunotherapy with LAK cells may be an effective treatment for patients with non-Hodgkin's lymphoma and merits further testing with larger numbers of patients in phase II trials.

Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

2004 ◽  
Vol 22 (20) ◽  
pp. 4095-4102 ◽  
Author(s):  
Nam H. Dang ◽  
Fredrick B. Hagemeister ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Jorge E. Romaguera ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Stable Disease ◽  
Hodgkin’S Lymphoma ◽  
Phase Ii Study ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Denileukin Diftitox ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. Patients and Methods Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 μg/kg once daily for 5 days every 3 weeks, up to eight cycles. Results Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25− histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. Conclusion Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25− B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.

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