Gero Hütter

Gero Hütter
Cellex

MD, PhD

About

77
Publications
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4,288
Citations

Publications

Publications (77)
Article
Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tr...
Article
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention that has led to an HIV cure. Whereas the HIV reservoir sharply decreases after allo-HSCT, the dynamics of the T cell reconstitution has not been comprehensively described. We analyzed the activation and differentiation of CD4 ⁺ and CD8 ⁺ T cells, and the...
Article
Full-text available
Der Fall einer dauerhaften Heilung von HIV nach allogener Stammzelltransplantation im Jahre 2007 an der Charité Berlin erzeugte damals ein breites Medienecho. Was ist seither geschehen? Wie geht es dem Patienten? Sind neue Fälle dazugekommen? Welchen Einfluss auf die HIV-Forschung hatte dieses Ereignis? Diese Fragen werden im folgenden Beitrag bean...
Article
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Due to the limited self-healing capacity of articular cartilage, innovative, regenerative approaches are of particular interest. The use of two-stage procedures utilizing in vitro expanded mesenchymal stromal cells (MSCs) from various cell sources requires good manufacturing practice-compliant production, a process with high demands on time, staffi...
Chapter
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Transfusion-related infectious complications have been become infrequent since the introduction of highly sensitive nucleotide acid tests and the nearly complete removal of residual leukocytes from the product. Last option is not feasible in stem cell products, and it should be assumed that this is associated with noteworthy side effects. Furthermo...
Article
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HIV-1 can persist in a latent form in resting memory CD4+ cells and macrophages carrying an integrated copy of the HIV genome. Because of the presence of these stable reservoir cells, eradication by antiretroviral therapy is unlikely and in order to achieve eradication, alternative treatment options are required. Stem cell transplantation has been...
Article
Full-text available
Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use...
Article
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A 32 base pair deletion in the c-c chemokine receptor gene 5 (CCR5) leads to an inactive protein. Carriers of this deletion must have had a selective advantage because the allelic frequency of the CCR5-delat32 mutation is much higher than expected. Furthermore, there is a decline from North to South Europe. For Germany there are just very few cross...
Article
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Ursache des oberen Ileus in der Gastroduodenoskopie.© G. Hütter _ Eine 78-jährige, extrem adipöse Patientin (135 kg bei 154 cm Körpergröße) wurde vom Hausarzt wegen seit drei Tagen bestehenden, nicht blutigen, unstillbaren Erbrechens eingewiesen. Diarrhöen bestanden nicht. Als Vorerkrankung waren neben der Adipositas permagna eine Herzinsuffizienz...
Chapter
Full-text available
HIV-1 can persist in a latent form in resting memory CD4+ cells and macrophages carry an integrated copy of the HIV genome. Because of the presence of these stable reservoir cells, eradication by antiretroviral therapy is unlikely, and in order to achieve eradication, alternative treatment options are required. Recently, we have described a success...
Article
Full-text available
During the last decade, Sangamo a biotech company located in Richmond (CA, USA), developed a specific ZFN that induces a double-strand break in the CCR5 gene, leading to a nonfunctional receptor and thereby mimicking the natural occurring CCR5-Δ32 deletion. However, a complete suppression of all CCR5 expression on the cell surface is not feasible w...
Article
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The “Berlin patient” is the first patient cured of HIV-1 infection after allogeneic transplantation with nonfunctional CCR5 coreceptor stem cells. We demonstrate that CXCR4-predicted minority viruses present prior to transplantation were unable to rebound after transplantation due to their dependence on CCR5 for replication and high genetic barrier...
Article
Full-text available
Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a...
Article
Full-text available
Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)–infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Ant...
Article
Full-text available
CCR5-delta32 heterozygous individuals are susceptible to HIV-1. However, it is not clear if there is a relevant protective effect against transmission and a beneficial effect in terms of HIV progression which cannot be attributed to CCR5 surface density alone. Therefore we investigated HIV-1 dependency factors (HDF) which might be differently regul...
Article
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There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samp...
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Investigation of X-chromosome inactivation patterns (XCIP) by determination of differential CpG-methylation has been widely applied for investigation of female cell clonality. Using this approach the clonal origin of various tumours has been corroborated. Controversially, strong age-related increase of peripheral blood (PB) cell clonality in haemat...
Article
Full-text available
Infection with the human immunodeficiency virus type 1 (HIV-1) causes a continuous decrease of T-cells ending in the acquired immune deficiency syndrome (AIDS). HIV-1 requires the presence of a CD4 receptor and a chemokine receptor, namely CCR5. The most encouraging method of interrupting the interaction of the viral surface glycoprotein gp120 with...
Article
1694 Introduction Myelodysplastic syndromes are a heterogeneous group of malignant clonal hematologic disorders characterized by ineffective hematopoiesis, peripheral cytopenias and dysplastic bone marrow cells, with frequent progression to acute myeloid leukemia. Because of its heterogeneous nature, modeling of this disease has proven to be very...
Article
To search for new copy number alterations (CNAs) in acute promyelocytic leukemia (APL), we analyzed DNA from leukemic blasts of 93 acute promyelocytic leukemia (APL) patients with Genome-Wide SNP 6.0 arrays (SNP-A). We identified 259 CNAs consisting of 170 heterozygous deletions, 82 amplifications, and 7 regions of copy number neutral loss of heter...
Chapter
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The survival of patients infected with human immunodeficiency virus type 1 (HIV-1) has considerably improved since the introduction of antiretroviral therapy (HAART). However, therapy is associated with serious problems, including toxic side effects, and the mortality rate is high among HIV-1-infected patients who are unable to receive HAART or hav...
Article
420 Introduction The characteristic hallmark of acute promyelocytic leukemia (APL) is a balanced reciprocal chromosomal translocation between chromosomes 15 and 17 leading to a fusion product consisting of the promyelocytic leukemia gene (PML) and the retinoic acid receptor alpha (RARA). The PML-RARA fusion product is necessary but not sufficient...
Article
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The natural function of the C-C chemokine receptor type 5 (CCR5) is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32) located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in...
Article
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Today, 30 years after the appearance of the HIV pandemic, treatment strategies have considerably improved but there is still no cure for this disease available. Recently, we have described a successful haematopoietic stem cells transplantation in an HIV-1 infected patient applying donor cells with a natural resistance against this infection. These...
Article
Full-text available
Humans respond differently toward exposure against pathogens and some individuals are completely resistant against transmission due to a genetically determined susceptibility. A rising number of such, so-called, host factors have been described during the last years, but their role for diagnostic or therapeutic application is still to be clarified....
Article
Full-text available
Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1-infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hemat...
Article
For treatment of several malignancies, transplantation of allogeneic haematopoietic stem cells (HSCT) derived from bone marrow or peripheral blood has been used as a therapeutic procedure for decades. In the past, HSCT has been suggested as a treatment option for infection with the human immunodeficiency virus type 1 (HIV-1), but these attempts wer...
Article
Full-text available
HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the lo...
Article
The analysis of genomic alterations in acute lymphoblastic leukemia (ALL) has provided new insights for prognosis and possible targets of novel therapies. In T-ALL the role of molecular abnormalities has still to be determined. Deregulated promoter hypermethylation of critical genes like PAX5 may have a significant impact on the course of ALL. Samp...
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Invasive pulmonary aspergillosis (IPA) represents ~ a major cause of morbidity and mortality in patients I with impaired function of the immune system such as in patients with acute myeloid leukaemia (AML). We investigated the in uence of the patients’ room occu- pancy and the sanitary facilities with regard to the inci- dence of IPA after reconstr...
Article
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Interaction with the chemokine receptor, CCR5, is a necessary precondition for maintaining HIV-1 infection. Individuals with the CCR5-delta32 deletion who lack this receptor are highly resistant to infection by the most common forms of HIV-1. We recently reported on the successful transplantation in an HIV-1-positive patient of allogeneic stem cell...
Article
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Changes of the peripheral blood cell count in patients with anorexia nervosa (AN) are frequent. Anemia and leukopenia are observed in one-third of these patients. Examination of the bone marrow reveals in almost 50% of the patients with AN signs of bone marrow atrophy and can additionally suffer from a gelatinous bone marrow transformation. Publish...
Article
Full-text available
Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a...
Article
Full-text available
When comparing myelogenous blasts from bone marrow and peripheral blood, immunophenotyping usually show a strong correlation of expression of surface antigens. However, it remains to be determined, whether this correlation also exists on the level of protein expression. Therefore, we investigated both bone marrow and peripheral blood blast cells fr...
Article
Over a long period of time, the impact of inhibiting angiogenesis as an option to treat malignancies, has been uncertain. Since the introduction of bevacizumab in the therapy of colorectal cancer, the mechanism and understanding of angiogenesis have become an important module in cancer treatment. Here we describe a new way of inhibiting angiogenesi...
Article
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Several intracytoplasmic morphological changes in the plasma cells of multiple myeloma have been described previously. However, Auer rod-like inclusions are rarely found in these types of cells. Here, we report a case of multiple myeloma with Auer rod-like, needle-shaped intracytoplasmic inclusions in plasma cells. A review of all published cases r...
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This study was performed to investigate hematotoxicity and occurrence of PPE in patients with high-grade non-Hodgkins lymphoma treated with a modified CHOP regimen (CLAOP), where doxorubicin had been substituted by a noncardiotoxic pegliposomal doxorubicin. An open-label phase I/IIa study was performed evaluating CLAOP21/20 with 20 mg/m(2) of pegli...
Article
The purpose of this study was to assess the efficacy and safety of pegylated liposomal doxorubicin in combination with cyclophosphamide and dexamethasone (CLAD). In this prospective open-label phase II study, 60 patients with advanced multiple myeloma (MM) received three weekly cycles of CLAD, consisting of cyclophosphamide 200 mg/m2 i.v. d1-4, peg...
Article
17548 Background: CHOP combination chemotherapy is the most effective and least toxic regimen for high-grade Non-Hodgkin’s-lymphoma (NHL). Doxorubicin, however, presents a problem in patients at risk for cardiotoxicity. Pegliposomal doxorubicin is a liposomal preparation of doxorubicin with minimal cardiotoxicity. In the CLAOP regimen reported here...
Article
9563 Objectives: The current first line standard chemotherapy for advanced soft-tissue sarcomas is the combination of doxorubicine and ifosfamide. Liposomal encapsulation is a strategy pursued to reduce toxicity and improve tumor uptake. There are so far only limited systematic data regarding the efficacy of liposomal anthracyclines in advanced sof...
Article
The anthracycline/ifosfamide combination is the most effective chemotherapy in soft tissue sarcoma. To improve the tolerability and potential efficacy of this combination, the authors combined a moderate dose of continuous infusion ifosfamide with liposomal daunorubicin (L-Dauno). In a single-arm, Phase II study, 40 patients with a median age of 57...
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Oxaliplatin and topotecan are novel options for a variety of neoplasms. Topotecan has shown fewer side effects and higher efficacy when given as a continuous i.v. infusion compared to single doses, but this regimen has not yet been combined with oxaliplatin. This phase I/II trial was designed to establish the dose-limiting toxicity of a combination...
Article
6708 Background: CHOP is the standard combination chemotherapy for high-grade Non-Hodgkin's-lymphoma (NHL). Pegliposomal doxorubicin in comparison to free doxorubicin has minimal cardiotoxicity. We performed a phase I/II study of a modified CHOP regimen including pegliposomal doxorubicin, termed CLAOP, in patients with high-grade NHL and cardiac ri...
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Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer. Patients with...
Article
Malignant melanomas have poor prognosis since treatment with anti-neoplastic agents is mostly ineffective. The biological mechanisms of this strong intrinsic therapy resistance are unknown. In order to identify new molecular factors potentially associated with the drug-resistant phenotype of malignant melanoma, a panel of human melanoma cell varian...
Article
Extensive studies during the last decades have identified several mechanisms through which cells escape the cytotoxic effects of a variety of chemotherapeutic drugs. One type of drug resistance is called multidrug resistance (MDR), because selection with one anticancer drug leads to cross-resistance with a wide range of other drugs. These MDR cells...
Article
A model system for studying chemoresistance in human melanoma cells (MeWo) has been established utilizing the four commonly used cytotoxic drugs vindesine, cisplatin, fotemustine and etoposide to yield stable drug-resistant sublines. We analyzed phenotypical differences between MeWo cells and their chemoresistant counterparts using two-dimensional...
Thesis
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Die Therapie von disseminierten malignen Tumoren durch Chemotherapie allein oder in Kombination mit Bestrahlung oder Hyperthermie führt nur in 20-50% zu einem Ansprechen. Dieser Behandlungserfolg wird häufig dadurch limitiert, daß im Verlauf der Therapie zur Entwicklung einer Chemoresistenz kommt. Ziel der Arbeit war es, eine generelle Analyse der...
Article
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In order to study possible mechanisms leading to chemoresistance in pancreatic adenocarcinoma we examined the global protein expression of pancreatic cancer cells in vitro. We used a cell culture model derived from the adenocarcinoma of the pancreas (EPP85-181P). A classical multidrug-resistant subline, EPP85-181RDB, selected in presence of daunoru...
Article
In search of novel mechanisms that may lead to the development of chemoresistance of malignant tumors of the large bowel we used two-dimensional electrophoresis to identify proteins that were overexpressed in colorectal and fibrosarcoma cell lines that were resistant towards mitoxantrone. This cytostatic drug is known to lead to atypical multidrug...
Article
The therapy of advanced cancer using chemotherapy alone or in combination with radiation or hyperthermia yields an overall response rate of about 20-50%. This success is often marred by the development of resistance to cytostatic drugs. Our aim was to study the global analysis of protein expression in the development of chemoresistance in vitro. We...

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