Selective responsiveness to common gamma chain cytokines in peripheral blood-derived cytotoxic T lymphocytes induced by Melan-A/MART-127-35targeted active specific immunotherapy

2005 ◽  
Vol 115 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Urs von Holzen ◽  
Michel Adamina ◽  
Martin Bolli ◽  
Walter P. Weber ◽  
Paul Zajac ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Specific Immunotherapy ◽  
Gamma Chain ◽  
Common Gamma Chain ◽  
Active Specific Immunotherapy

Clonal analysis of in vivo activated CD8+ cytotoxic T lymphocytes from a melanoma patient responsive to active specific immunotherapy

1993 ◽  
Vol 37 (1) ◽  
pp. 15-25 ◽  
Author(s):  
June Kan-Mitchell ◽  
Xiu Qing Huang ◽  
Lawrence Steinman ◽  
Jorge R. Oksenberg ◽  
William Harel ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Melanoma Patient ◽  
Specific Immunotherapy ◽  
Clonal Analysis ◽  
Active Specific Immunotherapy

PERSPECTIVES IN ACTIVE SPECIFIC IMMUNOTHERAPY WITH AUTOLOGOUS IMMATURE DENDRITIC CELLS COMBINED WITH PHOTODYNAMIC THERAPY AND CYCLOPHOSPHAMIDE IN PATIENTS WITH DISSEMINATED MELANOMA RESISTANT TO STANDARD THERAPY

2017 ◽  
Vol 63 (2) ◽  
pp. 336-345
Author(s):  
Irina Baldueva ◽  
N. Avdokina ◽  
Aleksey Belyaev ◽  
Aleksandr Shcherbakov ◽  
Tatyana Semiglazova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Photodynamic Therapy ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Standard Therapy ◽  
Specific Immunotherapy ◽  
Active Specific Immunotherapy ◽  
Dc Vaccine ◽  
Immature Dendritic Cells ◽  
Melanoma Patients

There are described the results of clinical and immunological efficacy assessment of active specific immunotherapy with autologous immature dendritic cells (DC) combined with photodynamic therapy (PDT) and cyclophosphamide (C) in disseminated melanoma patients, resistant to standard therapy. 27 patients treated in the N.N. Petrov Research Institute of Oncology were included in the study from 2007 till 2016. Immunotherapy was conducted in a 21-day cycles. Therapy included following steps: 1) preparation of individual vaccine preparation from bone-marrow derived DC with immune phenotype CD34-/CD14VCD1a+/CD83VCD80-/+/CD86-/+/HLA-DR+; 2) Intramuscular 300 mg C injection in day 1 of treatment cycle for elimination T-lymphocytes with immunosuppressing activity; 3) PDT with chlorin salts at day 4 six hours before start of vaccinotherapy; 4) Daily intralesional injections of DC vatccine in irradiated lesions in the dose 1х106 DC cells/ kg. Clinical and immunological efficacy was assessed in 27 patients. Fourteen (52%) patients received 1-2 cycles of therapy, 13(48%) received 3 or more cycles. No complete response was seen. Partial response (RECIST 1.1) was found in 2 (7,4%) patients, stable disease in 8 (29,6%) patients. Seventeen (63%) patients progressed. Median time to progression (TTP) was 2.5 month, median overall survival (OS) 8.4 month. One-year survival was 5% and 37% for TTP and OS, respectively. No adverse events (AE) of grade 4-5 (CTC AE v4) were seen. Grade 3 fever was registered in 4% of patients. Grade 1-2 AE were found in 54% of patients. Immunologic assessment revealed significant decline of immunoregulatory index (CD/ CD8) caused by prevalence of cytotoxic T-lymphocytes in peripheral blood of responding patients (patients with clinical benefit). Tendency for elevation of absolute number of activates T-helpers and cytotoxic T-lymphocytes together with low T-regulatory cells concentration was also found. Combination therapy using immunomodulatory effects of C, PDT and DC vaccine in 21-day treatment cycles produce promising activity and favorable toxicity profile in heavily pretreated disseminated melanoma patients.

SV40 Tag-specific cytotoxic T lymphocytes generated from the peripheral blood of malignant pleural mesothelioma patients

2002 ◽  
Vol 50 (12) ◽  
pp. 682-690 ◽  
Author(s):  
Robert K. Bright ◽  
Eric T. Kimchi ◽  
Michael H. Shearer ◽  
Ronald C. Kennedy ◽  
Harvey I. Pass
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Malignant Pleural Mesothelioma ◽  
Peripheral Blood ◽  
Pleural Mesothelioma

Frequency analysis of tumor-reactive cytotoxic T lymphocytes in peripheral blood of a melanoma patient vaccinated with autologous tumor cells

1994 ◽  
Vol 39 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Wolfgang Herr ◽  
Thomas W�lfel ◽  
Michael Heike ◽  
Karl-Hermann Meyer zum B�schenfelde ◽  
Alexander Knuth
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Frequency Analysis ◽  
Peripheral Blood ◽  
Melanoma Patient ◽  
Autologous Tumor

The Clinical Use of Donor-Derived Virus-Specific Cytotoxic T Lymphocytes Reactive Against Cytomegalovirus (CMV), Adenovirus and Epstein Barr Virus (EBV).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 81-81
Author(s):  
Doug Myers ◽  
Ann M. Leen ◽  
Ulahan Sili ◽  
Mary H. Huls ◽  
Elizabeth Buza ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Dose Level ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Clinical Manifestations ◽  
Normal Donor ◽  
Specific Lysis ◽  
Peptide Epitopes ◽  
Post Transplant

Abstract CMV, Adenovirus and EBV are major viral pathogens causing morbidity and mortality in immunocompromised patients undergoing allogeneic stem cell transplantation. Previous studies have shown that prophylactic adoptive immunotherapy with donor-derived Cytotoxic T Lymphocytes (CTL) directed against EBV and CMV can effectively prevent the clinical manifestations of these viruses. We have extended these studies by generating CTL from normal donor PBMC that can restore cellular immunity to CMV, EBV and adenovirus simultaneously. We have developed a protocol utilizing an initial round of stimulation with autologous mononuclear cells transduced with a recombinant adenovirus type 5 vector pseudotyped with a type 35 fiber carrying a transgene for the immunodominant CMV antigen, pp65 (Ad5f35pp65). This is followed by 2 rounds of weekly stimulation with autologous EBV-lymphoblastoid cell lines (LCL) transduced with the same vector using MOIs of 10 and 100 respectively. After 3 rounds of stimulation, 9 CTL cultures contained a mean of 83% (range 8.4–98.99%) CD8+ve and a mean of 19.6% (range 2.2–91.6%) CD4+ve cells. In chromium release and/or IFNg ELISPOT assays, all CTL lines showed specific activity against CMV and EBV targets. 8/9 lines also showed specific lysis against adenovirus targets. Further, using MHC-peptide multimers we have been able to demonstrate the simultaneous presence of CD8+ve cells recognizing peptide epitopes from CMV pp65 (range 2.32–21%) and Adenovirus hexon (1.07–8.08%) in the CTL cultures. So far we have treated 6 patients in this phase I CMV prophylaxis study, 3 on dose level 1 (1x10e7/m2) and 3 on dose level 2 (5x10e7/m2). Patients received 1 infusion of virus-specific CTL from 54–120 days post transplant. We observed up to a 28-fold increase in CMV pentamer positive CD8+ve cells post CTL. At last follow-up (7–35 weeks post CTL infusion) all patients are CMV and EBV negative. 2 patients were transiently positive for CMV by PCR 4–9 weeks post CTL but both were negative 7 days later without anti-viral therapy, with a corresponding rise in CMV-specific CTL detected in the peripheral blood. 2 patients were culture positive for adenovirus in their stool pre CTL therapy. One of these patients was infected with adenovirus species from subgroups A, C and D. In both patients, we observed a 2-log reduction of adenovirus copies/g stool within 2–3 weeks post CTL infusion at which time their symptoms (fever, loose stools) resolved. In summary, we have developed a protocol for the efficient generation of multi-virus specific CTL: infusion of small numbers of these cells increased virus-specific CD8+ve T cells in the peripheral blood post CTL infusion. Further, reduction in adenovirus load in stool suggests efficacy of adenovirus specific CTL in vivo. However, expansion of virus-specific CTL in vivo may require presence of antigen. We will therefore complete this prophylaxis study and then proceed to using virus-specific CTL for the treatment of CMV and adenovirus disease post transplant.

Two forms of the T-cell receptor γ protein found on peripheral blood cytotoxic T lymphocytes

Nature ◽  
1987 ◽  
Vol 325 (6106) ◽  
pp. 689-694 ◽  
Author(s):  
Michael B. Brenner ◽  
Joanne McLean ◽  
Harriet Scheft ◽  
Janice Riberdy ◽  
Siew-Lan Ang ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Cell Receptor
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