scholarly journals Distinctions Between Effective and Ineffective AML-Specific Autologous Peripheral Blood (PB) Cytotoxic T-Lymphocytes (CTLs)

2015 ◽  
Vol 21 (2) ◽  
pp. S190-S191
Author(s):  
Rohtesh S. Mehta ◽  
Xiaohua Chen ◽  
Jeyaraj Antony ◽  
Paul Szabolcs
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood

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

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

Generation of tumor-specific cytotoxic T-lymphocytes from peripheral blood of colorectal cancer patients for adoptive immunotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3056-3056
Author(s):  
Marco Bregni ◽  
Serena Del Bue ◽  
Andrea Galli ◽  
Alberto della Valle ◽  
Pasquale Ferrante ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Tumor Cell Line ◽  
Interleukin 4 ◽  
Autologous Tumor ◽  
The Third ◽  
Ifn Γ

3056 Background: Adoptive T-cell transfer (ACT) using autologous TIL, grown ex vivo and then infused into the cancer patient after lymphoablative chemotherapy, has emerged as an effective treatment for patients with metastatic melanoma. However, this approach has been hampered by the difficulty of isolating TILs from tumors other than melanoma, and of amplifying a sufficient quantity of autologous tumor-reactive T cells. So we decided to adopt a recently described procedure for generating in vitro large numbers of anti-tumor HLA-restricted CTLs, by stimulating patient’s CD8-enriched peripheral blood mononuclear cells (PBMCs) with DCs pulsed with apoptotic solid tumor cells (TCs) as a source of tumor antigens. Methods: 61 patients affected by CRC were enrolled. Tumor biopsies were obtained at surgery, together with 100 ml of heparinized peripheral blood. Tumors were dissociated to a single-cell suspension and cultured in order to obtain tumor cell line from each patient. Dendritic cells (DCs) were generated from previously separated PBMCs, using a magnetic positive selection of CD14+ monocytes, cultured in presence of Interleukin-4 and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Anti-tumor cytotoxic T lymphocytes (CTLs) were elicited using DCs as antigen-presenting cells, autologous apoptotic tumor cells as source of antigens and T CD-8 lymphocytes enriched effectors, with weekly stimulation. To evaluate the cytotoxic activity of CTLs, interferon-γ (IFN-γ) secretion was assessed by ELISPOT. Results: Tumor cell lines and DCs were obtained from 19 out of 61 patients. ELISPOT was performed so far for 6 patients: strong IFN-γ secretion was detected at the third, fourth and fifth stimulations for one patient and at the second for another patient, whereas for three patients a weak secretion was detected during the second and the third stimulations. CTLs from one patient did not react to the stimulations. Conclusions: Generation of CTLs suitable for ACT immunotherapy is feasible from peripheral blood in patients with CRC.

scholarly journals Low Frequency of Cytotoxic T Lymphocytes against the Novel HLA-A*0201-Restricted JC Virus Epitope VP1p36 in Patients with Proven or Possible Progressive Multifocal Leukoencephalopathy

2003 ◽  
Vol 77 (22) ◽  
pp. 11918-11926 ◽  
Author(s):  
Renaud A. Du Pasquier ◽  
Marcelo J. Kuroda ◽  
Joern E. Schmitz ◽  
Yue Zheng ◽  
Kristi Martin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Jc Virus ◽  
The Novel ◽  
Tetramer Staining ◽  
Cellular Immune

ABSTRACT JC virus (JCV)-specific cytotoxic T lymphocytes (CTL) in peripheral blood are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML). However, the frequency of these cells in the peripheral blood mononuclear cells (PBMC) of PML patients is unknown. To develop a highly sensitive assay for detecting the cellular immune response against this virus, we performed a CTL epitope mapping study of JCV VP1 major capsid protein by using overlapping peptides. A novel HLA-A*0201-restricted epitope, the VP1p36 peptide SITEVECFL, was characterized. The cellular immune response against JCV was assessed in 32 study subjects. By combining the results of the 51Cr release assay on pooled peptides and staining with the HLA-A*0201/JCV VP1p36 tetramer, VP1-specific CTL were detected in 10 of 11 PML survivors (91%) versus only 1 of 11 PML progressors (9%, P = 0.0003). VP1-specific CTL were also detected in two of two patients recently diagnosed with PML and in four of four human immunodeficiency virus-positive patients with possible PML. The frequency of CTL specific for the novel VP1p36 and the previously described VP1p100 epitopes was determined. In two patients, the frequency of CTL specific for the VP1p36 or VP1p100 epitopes, as determined by fresh blood tetramer staining (FBTS), ranged from 1/6,000 to 1/24,000 PBMC. A CTL sorting technique combining tetramer staining and selection with immunomagnetic beads allowed the detection of epitope-specific CTL in two cases that were determined to be negative by FBTS. The phenotype of these CTL in vivo was consistent with activated memory cells. These data suggest that, although present in low numbers, JCV-specific CTL may be of central importance in the containment of JCV spread in immunosuppressed individuals.

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