23 results on '"Weihrauch, Martin R."'
Search Results
2. Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of patients with epithelial malignancies
- Author
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Weihrauch, Martin R., Skibowski, Edmund, Draube, Andreas, Geller, Andrea, Tesch, Hans, Diehl, Volker, and Bohlen, Heribert
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- 2002
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3. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma
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Klein-González, Nela, Holtick, Udo, Fairfax, Kirsten, Weihrauch, Martin R, and von Bergwelt-Baildon, Michael S
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- 2011
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4. Complete Remission in a Colon Cancer Patient with a Large, Irresectable Liver Metastasis after XELOX/Cetuximab/Bevacizumab Treatment
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Weihrauch, Martin R., Stippel, Dirk, Fries, Jochen W.U., Arnold, Dirk, Bovenschulte, Henning, Coutelle, Oliver, and Hacker, Ulrich
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- 2008
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5. Immunomagnetic Enrichment and Detection of Micrometastases in Colorectal Cancer: Correlation With Established Clinical Parameters
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Weihrauch, Martin R., Skibowski, Edmund, Koslowsky, Thomas C., Voiss, Wilfried, Re, Daniel, Kuhn-Regnier, Ferdinand, Bannwarth, Carolin, Siedek, Michel, Diehl, Volker, and Bohlen, Heribert
- Published
- 2002
6. Retrobulbar, Intracranial, and Cutaneous Secondary Plasmacytomas in a Patient with Atypical Multiple Myeloma
- Author
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Weihrauch, Martin R. and Diehl, Volker
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- 2001
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7. Thoracic positron emission tomography using18F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease
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Weihrauch, Martin R., Re, Daniel, Scheidhauer, Klemens, Ansén, Sascha, Dietlein, Markus, Bischoff, Stefanie, Bohlen, Heribert, Wolf, Jürgen, Schicha, Harald, Diehl, Volker, and Tesch, Hans
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- 2001
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8. Ultrasound-guided core needle biopsies for workup of lymphadenopathy and lymphoma.
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Groneck, Laura, Quaas, Alexander, Hallek, Michael, Zander, Thomas, and Weihrauch, Martin R.
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LYMPHADENITIS ,LYMPHOMAS ,CORE needle biopsy ,NEEDLE biopsy ,CARCINOMA ,DIAGNOSIS ,PATIENTS ,THERAPEUTICS - Abstract
Background For the histopathological diagnosis of lymphoma, lymph node excision biopsies are regarded as standard of care. In contrast, for the diagnosis of carcinoma and deep-seated tumors, core needle biopsies ( CNBs) are accepted as a sufficient sampling method. We evaluated a diagnostic algorithm for peripheral lymphadenopathy starting with ultrasound-guided CNB followed by excisional biopsy in ambiguous cases. Methods We performed ultrasound-guided CNB of peripheral lymph nodes and subcutaneous tumors in patients with lymphadenopathy in routine care and analyzed its accuracy, complication rate, and the impact of needle sizes on results. Results From 138 patients, 132 samples were technically adequate. In 121 patients, CNB provided a clinically actionable diagnosis (76 lymphoma, 30 carcinoma, 15 non-malignant diagnoses). A total of 54 patients had a secondary biopsy. Inconclusive diagnoses were rare with two false-positive and two false-negative non-Hodgkin's lymphoma, and higher for Hodgkin's lymphoma with five false-negative cases. The rate of complications was low. Needle size did not significantly influence results. Conclusion Ultrasound-guided CNBs are a safe, quick, and valid tool for the workup of lymphadenopathy. Yet, a benign diagnosis from CNB must be completed by a secondary biopsy if clinical presentation suggests malignant disease. [ABSTRACT FROM AUTHOR]
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- 2016
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9. Phase I clinical study of the toll-like receptor 9 agonist MGN1703 in patients with metastatic solid tumours.
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Weihrauch, Martin R., Richly, Heike, von Bergwelt-Baildon, Michael S., Becker, Hans Jiro, Schmidt, Manuel, Hacker, Ulrich T., Shimabukuro-Vornhagen, Alexander, Holtick, Udo, Nokay, Bahar, Schroff, Matthias, Wittig, Burghardt, and Scheulen, Max E.
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DNA , *TREATMENT of lung tumors , *SUBCUTANEOUS injections , *CANCER patients , *CELL receptors , *DRUG side effects , *IMMUNOLOGICAL adjuvants , *METASTASIS , *TREATMENT duration , *THERAPEUTICS - Abstract
Purpose This study was initiated to evaluate safety, toxicity, pharmacokinetics, and pharmacodynamics of treatment with MGN1703, a novel synthetic DNA-based toll-like receptor 9 (TLR9)-immunomodulator. Methods The study consisted of an escalating single dose regimen followed by a multiple dose part. Dose levels of 0.25, 2, 10, 30, and 60 mg of MGN1703 were administered subcutaneously over 6 weeks twice weekly. Patients with at least stable disease (SD) could participate in the extension phase of the study for six further weeks. Effects on the immune status were monitored. Results 28 patients with metastatic solid tumours were included. Fatigue and activated partial thromboplastin time (aPTT) prolongation were the only two cases of drug-related grade 3 Common Terminology Criteria adverse events (CTCAE). The most frequently reported drug-related adverse events were of CTC Grade ⩽2. There was no relationship between toxicity and dose and no patient was withdrawn from the study due to drug-related AE. No drug-related serious AE (SAE) were reported. Six out of 24 patients had SD after 6 weeks of treatment and three of those remained in SD after a total of 12 weeks. Four patients were further treated in a compassionate use programme showing long-term disease stabilisation for up to 18 months. Immune assessment of cell compartments showed a non-significant increase of TLR9 expressing naïve B cells during therapy. Conclusion Twice weekly subcutaneous applications of MGN1703 in a dose of up to 60 mg are safe and well tolerated without dose-limiting toxicities. MGN1703 shows immune activation and anti-tumour efficacy in heavily pretreated patients. The recommended dose of 60 mg twice weekly is currently used in a phase II trial in small cell lung cancer and a phase III trial in colorectal cancer patients. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Analysis of Tie2-Expressing Monocytes (TEM) in Patients With Colorectal Cancer.
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Goede, Valentin, Coutelle, Oliver, Shimabukuro-Vornhagen, Alexander, Holtick, Udo, Neuneier, Janina, Koslowsky, Thomas C., Weihrauch, Martin R., von Bergwelt-Baildon, Michael, and Hacker, Ulrich T.
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COLON cancer treatment ,GENE expression ,MONOCYTES ,NEOVASCULARIZATION inhibitors ,CANCER cells ,CYTOLOGY ,PHENOTYPES - Abstract
Tie2-expressing monocytes (TEM) promote tumor angiogenesis and growth in experimental cancer models. The role of TEM in cancer patients is unknown. We studied TEM in healthy volunteers and colorectal cancer (CRC) patients. Although TEM were detectable in the blood and tumor lesions of CRC patients, their frequency and functional phenotype showed no correlation with levels of angiopoietin-2 or vascular endothelial growth factor, microvessel density, tumor markers, tumor stage, or outcome of antiangiogenic therapy. These unexpected findings are at odds with murine tumor models and question the diagnostic or therapeutic value of TEM in human cancer. [ABSTRACT FROM AUTHOR]
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- 2012
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11. In vivo Expansion of Naïve CD4+CD25high FOXP3+ Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration.
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Beyer, Marc, Schumak, Beatrix, Weihrauch, Martin R., Andres, Bettina, Giese, Thomas, Endl, Elmar, Knolle, Percy A., Classen, Sabine, Limmer, Andreas, and Joachim L. Schultze
- Subjects
CANCER patients ,CELLULAR mechanics ,REGULATION of cell growth ,CANCER treatment ,GROWTH factors ,CELL receptors ,CYTOKINES - Abstract
Regulatory T cells (T
reg cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of Treg cells was established. In IL-2 treated cancer patients a further Treg -cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional Treg cells of a naïve phenotype - as determined by CCR7 and CD45RA expression - are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve Treg -cell pool. Higher frequencies of T-cell receptor excision circles in naïve Treg cells indicate IL-2 dependent thymic generation of naïve Treg cells as a mechanism leading to increased frequencies of Treg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine Treg cells after IL-2 administration. These results point to a more complex regulation of Treg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve Treg cells. [ABSTRACT FROM AUTHOR]- Published
- 2012
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12. Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD1271 and FOXP3.
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Beyer, Marc, Classen, Sabine, Endl, Elmar, Kochanek, Matthias, Weihrauch, Martin R., Debey-Pascher, Svenja, Knolle, Percy A., and Schultze, Joachim L.
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T cells ,LEUKEMIA ,TUMORS ,LYMPHOMAS ,MULTIPLE myeloma - Abstract
In recent years an increase of functional CD4
+ CD25+ reg ulatory T cells (Treg cells) has been established for patients with solid tumors, acute leukemias, and lymphomas. We have reported an expanded pool of CD4+ CD25high Treg cells in patients with chronic lymphatic leukemia (CLL), multiple myeloma (MM) as well as its premalignant precursor monoclonal gammopathy of undetermined significance (MGUS). In healthy individuals,low -level expression of CD127 on T cells in addition to the expression of FOXP3 has been associated with Treg cells. Here, we demonstrate that the expanded FOXP3+ T-cell population in patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and Hodgkin's disease are exclusively CD127low Treg cells and were strongly suppressive. A significant portion of CD127low FOXP3+ Treg cells expressed onlylow levels of CD25 suggesting that the previously reported expansion of CD25+ Treg cells underestimates the true expansion. The assessment of CCR7 and CD45RA expression on the expanded CD4+ CD127low FOXP3+ Treg cells revealed an increase of both naïve as well as central and effector memory Treg cells in peripheral blood. Our data strongly support superiority of combined CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further quantification of Treg cells in malignant diseases. [ABSTRACT FROM AUTHOR]- Published
- 2011
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13. Phase I/II Clinical Study of Topotecan and Cytarabine in Patients with Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia.
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Weihrauch, Martin R., Staib, Peter, Seiberlich, Bettina, Hoffmann, Martin, Diehl, Volker, and Tesch, Hans
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CANCER chemotherapy , *LEUKEMIA , *DRUG efficacy , *DNA topoisomerase I , *ACUTE myeloid leukemia , *MYELODYSPLASTIC syndromes , *DRUG toxicity - Abstract
Topotecan, a topoisomerase-I inhibitor is an active drug in the treatment of AML and MDS. To evaluate its toxicity and efficacy in a combination regimen with cytarabine, we conducted a clinical phase I/II trial in patients with relapsed acute myeloid leukemia (AML) or relapsed or newly diagnosed MDS RAEB, RAEB-t or CMML. Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were treated with 1.25 mg/m 2 topotecan as continuous intravenous infusion daily for 5 days and cytarabine 1.0 g/m 2 by infusion over 2 h daily for 5 days (TA). Cycles were repeated on day 28. The median observation time was 131 weeks (range: 36 - 196 weeks). A total of 37 cycles of TA were administered. In 1 patient, the dose of TA had to be reduced and in 1 patient, there was a treatment delay for the second cycle, both because of hematologic toxicity. The most frequent non-hematologic side-effect of TA was fever, which occurred in 17 patients (89%) with temperatures over 38°C. None of the patients died due to any treatment-related toxicities, but 2 patients (10%) died within 1 month due to disease progression. A CR was achieved in 7 patients (33%), 3 of whom were MDS and 4 AML. A partial remission was reported in 8 patients (38%), no change of disease in 2 patients (10%) and progressive disease in 4 patients (19%). The median remission duration was 18 weeks (range 2 - 161 weeks) for MDS patients and 11 weeks (range 2 - 49 weeks) for AML patients. The time to progression for patients of 60 years and older ( n = 10) was 16 weeks (range 2 - 49 weeks) and the survival was 32 weeks (range 2 - 119 weeks). TA is a feasible and efficacious chemotherapeutic combination for the treatment of MDS RAEB, RAEB-t, CMML and AML. For patients of 60 years and older, this regimen is also a safe option. [ABSTRACT FROM AUTHOR]
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- 2004
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14. Prognostic Significance of {sup18]F-fluorodeoxyglucose Positron Emission Tomography in Lymphoma.
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Weihrauch, Martin R., Dietlein, Markus, Schicha, Harald, Diehl, Volker, and Tesch, Hans
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POSITRON emission tomography , *LYMPHOMA diagnosis - Abstract
Today, many patients with lymphoma are cured by polychemotherapy and irradiation. However, residual masses are frequently observed after treatment and discrimination between vital tumor and inactive fibrotic tissue by computed tomography or magnetic resonance tomography is often not possible. [sup 18]F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a metabolic imaging modality that is able to detect active lymphoma lesions. The application of PET may play a crucial role in identifying patients with residual disease and contribute valuable prognostic information. To assess the prognostic implications of PET in the post-therapeutic setting, we performed a MedLine Search and reviewed the current available studies on this important issue together with our own data. [ABSTRACT FROM AUTHOR]
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- 2003
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15. MGN1703, a Novel TLR9-Agonist - Results of a Phase 1 Clinical Trial in Patients with Metastatic Malignancies.
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Weihrauch, Martin R, Schmidt, Manuel, Tschaika, Marina, Richly, Heike, von Bergwelt-Baildon, Michael S, Hacker, Ulrich, Shimabokuro-Vornhagen, Alexander, Wittig, Burghardt, and Scheulen, Max E
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- 2009
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16. In vivo expansion of naïve CD4+ CD25(high) FOXP3+ regulatory T cells in patients with colorectal carcinoma after IL-2 administration.
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Beyer M, Schumak B, Weihrauch MR, Andres B, Giese T, Endl E, Knolle PA, Classen S, Limmer A, and Schultze JL
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- Adult, Aged, CD4-Positive T-Lymphocytes drug effects, CTLA-4 Antigen metabolism, Colorectal Neoplasms metabolism, Female, Flow Cytometry, Glucocorticoid-Induced TNFR-Related Protein metabolism, Humans, Male, Middle Aged, T-Lymphocytes, Regulatory metabolism, CD4-Positive T-Lymphocytes metabolism, Colorectal Neoplasms drug therapy, Colorectal Neoplasms immunology, Forkhead Transcription Factors metabolism, Interleukin-2 therapeutic use, Interleukin-2 Receptor alpha Subunit metabolism, T-Lymphocytes, Regulatory drug effects
- Abstract
Regulatory T cells (T(reg) cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of T(reg) cells was established. In IL-2 treated cancer patients a further T(reg)-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional T(reg) cells of a naïve phenotype--as determined by CCR7 and CD45RA expression--are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve T(reg)-cell pool. Higher frequencies of T-cell receptor excision circles in naïve T(reg) cells indicate IL-2 dependent thymic generation of naïve T(reg) cells as a mechanism leading to increased frequencies of T(reg) cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine T(reg) cells after IL-2 administration. These results point to a more complex regulation of T(reg) cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve T(reg) cells.
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- 2012
- Full Text
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17. Toll-like receptor 9 agonists as cancer therapeutics.
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Holtick U, Scheulen ME, von Bergwelt-Baildon MS, and Weihrauch MR
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- Animals, Antineoplastic Agents therapeutic use, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, Clinical Trials as Topic, CpG Islands, Humans, Immunologic Factors therapeutic use, Neoplasms immunology, Neoplasms metabolism, Oligonucleotides immunology, Signal Transduction drug effects, T-Lymphocytes, Cytotoxic drug effects, T-Lymphocytes, Cytotoxic immunology, Toll-Like Receptor 9 immunology, Toll-Like Receptor 9 metabolism, Neoplasms drug therapy, Oligonucleotides pharmacology, Toll-Like Receptor 9 agonists
- Abstract
Introduction: Toll-like receptor 9 (TLR9) agonists, commonly referred to as CpG oligodeoxynucleotides (ODN), have been added to the arsenal of anti-cancer drugs as monotherapy or in combination with chemotherapy, radiotherapy and other immunotherapeutic approaches as they increase antigen presentation and boost anti-tumor T- and B-cell responses. Several synthetic TLR9 agonists have been developed for clinical grade use and displayed substantial efficacy in the preclinical and clinical models., Areas Covered: This review summarizes TLR9 signaling and the impact of TLR9 agonists on the immune response. The most recent experimental and clinical data are analyzed as well as the development of new TLR9 agonists in current clinical trials., Expert Opinion: Application of TLR9 agonists, in particular, combination strategies with chemo- or radiotherapy seem a promising and efficient immunotherapeutic approach in cancer patients even with refractory disease. Simultaneous application of TLR9 agonists aims at supporting the patient's immune response and overcoming specific immunosuppressant strategies developed by tumors. Combinatory approaches of the future might also seek for synergism of TLR9 agonists with other immunomodulatory strategies such as B-cell activation using the CD40-CD40L system.
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- 2011
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18. Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: implications for cancer immunotherapy.
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Kondo E, Maecker B, Weihrauch MR, Wickenhauser C, Zeng W, Nadler LM, Schultze JL, and von Bergwelt-Baildon MS
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- Antigen-Presenting Cells immunology, B-Lymphocytes immunology, B-Lymphocytes pathology, CD40 Antigens immunology, Colonic Neoplasms therapy, HLA-A Antigens metabolism, HLA-A2 Antigen, Humans, Interferon-gamma metabolism, Lymphoma, Mantle-Cell therapy, Peptide Fragments immunology, Colonic Neoplasms immunology, Cyclin D1 immunology, Immunotherapy, Lymphoma, Mantle-Cell immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1-derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells., Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay., Results: After screening, at least two naturally processed and presented HLA-A*0201-binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201-matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer., Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.
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- 2008
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19. T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals.
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Weihrauch MR, von Bergwelt-Baildon M, Kandic M, Weskott M, Klamp W, Rosler J, and Schultze JL
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- Adult, Carrier State epidemiology, Female, Global Health, Hepatitis B epidemiology, Hepatitis B immunology, Hepatitis B Vaccines therapeutic use, Humans, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Liver Cirrhosis immunology, Liver Cirrhosis mortality, Male, Middle Aged, Prevalence, Young Adult, Hepatitis B Surface Antigens blood, Hepatitis B Surface Antigens immunology, Hepatitis B Vaccines immunology, Liver Cirrhosis epidemiology, Lymphocyte Activation immunology, T-Lymphocytes immunology, Treatment Refusal
- Abstract
Aim: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccinees., Methods: Fourty-seven health care employees were enrolled in this study including all available non-responders (n = 13) with an anti-HBsAg titer < 10 kU/L and all available low-responders (n = 12) with an anti-HBsAg titer < 100 kU/L. Also, 12 consecutive anti-HBsAg negative pre-vaccination subjects were enrolled as well as 10 subjects (+7 from the vaccinated group) with titers > 1000 kU/L as controls. PBMC from all subjects were analyzed by IFN-gamma and IL-4 ELISPOT assays for the presence of hepatitis B surface antigen (HBsAg) reactive T cells., Results: Non-responders and low-responders had no or only very limited T cell responses, respectively. Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response after the third vaccination. Surprisingly, these individuals showed response even before the first vaccination. T cell response to control antigens and mitogens was similar in all groups., Conclusion: Our data suggest that there is no general immune deficiency in non-/low-responders. Thus, we hypothesize that the induction of anti-HBsAg responses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect.
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- 2008
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20. In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma.
- Author
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Beyer M, Kochanek M, Giese T, Endl E, Weihrauch MR, Knolle PA, Classen S, and Schultze JL
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- Antigens, CD blood, Antigens, CD genetics, CD4-Positive T-Lymphocytes pathology, Flow Cytometry, Forkhead Transcription Factors genetics, Forkhead Transcription Factors immunology, Humans, Leukocyte Common Antigens blood, Leukocyte Common Antigens genetics, Receptors, Antigen, T-Cell blood, Receptors, Antigen, T-Cell immunology, Receptors, CCR7, Receptors, Chemokine blood, Receptors, Chemokine genetics, CD4-Positive T-Lymphocytes immunology, Forkhead Transcription Factors blood, Multiple Myeloma blood, Multiple Myeloma immunology, Receptors, Interleukin-2 blood
- Abstract
In solid tumors, leukemias, and lymphomas, increased frequencies of functional CD4+CD25(high) regulatory T cells (T(reg) cells) have been previously demonstrated. In healthy individuals, T(reg) cells consist not only of memory but also of naive T cells, which can undergo peripheral expansion and are characterized by a relative enrichment for autoreactive T-cell receptors. Here, we demonstrate in patients with premalignant monoclonal gammopathy of undetermined significance and patients with multiple myeloma that functional FoxP3(+) T(reg) cells of naive, central, and effector memory phenotype as determined by CCR7 and CD45RA expression are significantly expanded. Low frequencies of T-cell receptor excision circles in naive T(reg) cells in both healthy controls and multiple myeloma patients point to peripheral expansion as the prominent mechanism of increased frequencies of naive T(reg) cells in these cancer patients. These findings strongly suggest that the increase of functional T(reg) cells in cancer patients is a response to the process of malignant transformation.
- Published
- 2006
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21. Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer.
- Author
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Weihrauch MR, Ansén S, Jurkiewicz E, Geisen C, Xia Z, Anderson KS, Gracien E, Schmidt M, Wittig B, Diehl V, Wolf J, Bohlen H, and Nadler LM
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- Adult, Aged, CD3 Complex analysis, CD4 Antigens analysis, CD8 Antigens analysis, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Carcinoembryonic Antigen blood, Colorectal Neoplasms immunology, Colorectal Neoplasms pathology, Combined Modality Therapy, Dose-Response Relationship, Drug, Female, Flow Cytometry, Fluorouracil administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Humans, Immunodominant Epitopes immunology, Immunotherapy methods, Interferon-gamma metabolism, Interleukin-2 administration & dosage, Irinotecan, Leucovorin administration & dosage, Liver Neoplasms immunology, Liver Neoplasms secondary, Liver Neoplasms therapy, Male, Middle Aged, Oligopeptides administration & dosage, Oligopeptides immunology, Prospective Studies, T-Lymphocytes cytology, T-Lymphocytes drug effects, T-Lymphocytes immunology, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoembryonic Antigen immunology, Colorectal Neoplasms therapy, HLA-A2 Antigen immunology, Oligopeptides therapeutic use
- Abstract
Purpose: We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen-derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells., Experimental Design: HLA-A2-positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity., Results: Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1-specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1-specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen-specific CD8+ cells decreased by an average 14%., Conclusions: The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination.
- Published
- 2005
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22. Elevated serum levels of CC thymus and activation-related chemokine (TARC) in primary Hodgkin's disease: potential for a prognostic factor.
- Author
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Weihrauch MR, Manzke O, Beyer M, Haverkamp H, Diehl V, Bohlen H, Wolf J, and Schultze JL
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- Adolescent, Adult, Aged, Chemokine CCL17, Enzyme-Linked Immunosorbent Assay, Female, Hodgkin Disease therapy, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Biomarkers, Tumor blood, Chemokines, CC blood, Hodgkin Disease blood
- Abstract
The CC thymus and activation-related chemokine (TARC) is a protein, which is highly expressed by Reed-Sternberg cells in Hodgkin's disease and is found in the majority of Hodgkin's disease patients. Within several trials conducted by the German Hodgkin study group, 62 Hodgkin's disease patients were elected based on availability of serum samples post and prior therapy to assess TARC levels by ELISA. TARC levels from 33 patients with continuous complete response (CCR), 20 patients with relapse, and nine patients with progressive disease (PD) were correlated with freedom from treatment failure and survival. As defined in healthy donors (mean value +/- 2x SD), a TARC level of >500 pg/mL was considered as elevated. The median TARC levels of all patients at baseline and after completed primary treatment were 5,803 pg/mL (range, 116-73,074 pg/mL) and 663 pg/mL (50-24,709 pg/mL), respectively. TARC levels of patients with PD were higher than those of patients with CCR at baseline and after therapy. Baseline TARC correlated significantly with stage (P = 0.019), erythrocyte sedimentation rate (P = 0.004), leukocyte count (P < 0.001), and lymphocyte count (P = 0.026). A TARC level of >2,000 pg/mL after completed treatment was a significant risk factor for poorer survival (P = 0.02) but not for relapse. In conclusion, monitoring serum TARC levels in Hodgkin's disease patients may add valuable information about therapy success in Hodgkin's disease patients, especially those with PD and should therefore be prospectively evaluated in future trials.
- Published
- 2005
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23. Carboxypeptidase-G2 rescue in cancer patients with delayed methotrexate elimination after high-dose methotrexate therapy.
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Krause AS, Weihrauch MR, Bode U, Fleischhack G, Elter T, Heuer T, Engert A, Diehl V, and Josting A
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- Adult, Antidotes administration & dosage, Female, Humans, Kidney Diseases chemically induced, Lymphoma complications, Lymphoma drug therapy, Male, Methotrexate blood, Methotrexate pharmacokinetics, Middle Aged, Neoplasms complications, Osteosarcoma complications, Osteosarcoma drug therapy, Treatment Outcome, Methotrexate toxicity, Neoplasms drug therapy, gamma-Glutamyl Hydrolase administration & dosage
- Abstract
High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G2 (CPDG2) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.
- Published
- 2002
- Full Text
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