Ingo G H Schmidt-Wolf

Centrum für Integrierte Onkologie, Köln, North Rhine-Westphalia, Germany

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Publications (164)688.82 Total impact

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    ABSTRACT: Cytokine-induced killer (CIK) cells represent an exceptional T cell population uniting a T cell and natural killer cell like phenotype in their terminally differentiated CD3(+)CD56(+) subset, which features non-MHC-restricted tumor-killing activity. CIK cells are expandable from peripheral blood mononuclear cells and mature following the addition of certain cytokines. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures. Therefore, we established the international registry on CIK cells in order to collect and evaluate data about clinical trials using CIK cells for the treatment of cancer patients. Moreover, our registry is expected to set new standards on the reporting of results from clinical trials using CIK cells. Clinical responses, overall survival (OS), adverse reactions and immunologic effects were analyzed in 45 studies present in our database. These studies investigated 22 different tumor entities altogether enrolling 2,729 patients. A mean response rate of 39 % and significantly increased OS, accompanied by an improved quality of life, were reported. Interestingly, side effects of CIK cell treatment were minor. Mild fevers, chills, headache and fatigue were, however, seen regularly after CIK cell infusion. Moreover, CIK cells revealed numerous immunologic effects such as changes in T cell subsets, tumor markers, cytokine secretion and HBV viral load. Due to their easy availability and potent antitumor activity, CIK cells emerged as a promising immunotherapy approach in oncology and may gain major importance on the prognosis of cancer.
    Journal of Cancer Research and Clinical Oncology 11/2014; · 2.91 Impact Factor
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    ABSTRACT: This largest prospective multicenter trial for adult patients with Burkitt lymphoma/leukemia aimed to prove efficacy and feasibility of a short-intensive chemotherapy combined with the anti-CD20 antibody Rituximab. 363 patients 16 to 85 years old (median 42 yrs) were recruited in 98 centers from 8/2002 until 06/2011. Treatment consisted of 6 five-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years received a reduced regimen. Rituximab was given d -1 before each cycle and twice as maintenance, for a total of 8 doses. The complete remission rate was 88% (319/363), the overall survival (OS) at 5 years 80%, and the progression-free survival (PFS) 71%, with significant difference between adolescents (≥15-25 yrs), adults (26-55 yrs) and elderly (>55 yrs) patients with an OS of 90%, 84%, and 62%. Full treatment could be applied in 86% of the patients. Most important prognostic factors were IPI (0-2 vs. 3-5, p=0.0005), aaIPI (0-1 vs. 2-3, p=0.0001), and gender (male vs. female, p=0.004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, also in elderly patients. The study is registered to www.clinicaltrials.gov as NCT00199082.
    Blood 10/2014; · 9.78 Impact Factor
  • Ilona Wall, Ingo G H Schmidt-Wolf
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    ABSTRACT: Activated Wnt signaling in cancer cells leads to cell proliferation. It has been shown that the Wnt pathway is activated in pancreatic adenocarcinoma cells. Therefore, we tested the effect of Wnt inhibitors in human and murine pancreatic cancer cell lines.
    Anticancer research 10/2014; 34(10):5375-80. · 1.71 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) is with an incidence of 4-6/100 000 inhabitants a fairly frequent malignancy of B cells. The incidence increases markedly with age. In this review changes in the treatment of relapsed / refractory myeloma during the last decade have been analysed. The present standard of care in the progressive or refractory myeloma was elaborated by the working group "Refractory Multiple Myeloma" using an extensive literature search for studies published between 2003 and 2013. Outside of clinical trials, high-dose therapy with stem cell transplantation is recommended in fit patients up to 75 years without significant comorbidities. Ongoing studies address the question about the least toxic and the most effective treatment. Therefore, inclusion of patients in therapeutic trials and use of novel agent combinations is highly recommended, e. g. with 3(rd) generation-IMIDs (pomalidomide), new proteasome inhibitors, such as carfilzomib, ixazomib or oprozomib, antibodies, such as elotuzumab, daratumumab or SAR650984, siltuximab, tabalumab, denosumab, romosozumab, BTK-, HSP-inhibitors and other innovative phase I/II agents. Conclusion: Based on new insights in the pathogenesis of the disease, treatment options for MM have changed significantly in recent years. There is a significantly larger treatment diversity, i. e. more MM-active agents and combinations are available today. Even with relapsed MM, patients with the disease often live longer and have fewer complications.
    Deutsche medizinische Wochenschrift (1946). 10/2014; 139(41):2091-2095.
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    ABSTRACT: Advanced renal cancer still has a very poor prognosis. In this regard recent investigations demonstrated a constitutive activation of the Wnt signaling pathway in renal cell carcinoma (RCC) thereby promoting an exaggerated cell proliferation. Especially, β-catenin overactivation and the functional loss of endogenous Wnt antagonists are associated with RCC carcinogenesis and progression. Thus, influencing Wnt signaling might represent a promising target in RCC treatment.
    Anticancer research 08/2014; 34(8):4101-8. · 1.71 Impact Factor
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    ABSTRACT: Aberrant activation of Wnt/β-catenin signaling promotes development and progression of various malignant neoplasms. Recent studies observed that the Wnt pathway is constitutively active in myeloma cells and promotes an exaggerated proliferation. Thus, the Wnt signaling pathway might be an attractive therapeutic target for multiple myeloma. In this study, we identified piceatannol as an inhibitor of the Wnt/β-catenin pathway and as a potent inducer of apoptosis in myeloma cells. Interestingly, healthy cells remained mainly unaffected. These results reveal a significant selective induction of apoptosis by piceatannol and suggest a significant in vivo effect against multiple myeloma. Copyright © 2014 John Wiley & Sons, Ltd.
    Hematological Oncology 01/2014; · 2.04 Impact Factor
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    ABSTRACT: Cytokine-induced killer (CIK) cells are a heterogeneous population of immune effector cells that feature a mixed T- and Natural killer (NK) cell-like phenotype in their terminally-differentiated CD3+CD56+ subset. The easy availability, high proliferation rate and widely major histocompatibility complex (MHC)-unrestricted antitumor activity of CIK cells contribute to their particularly advantageous profile, making them an attractive approach for adoptive immunotherapy. CIK cells have shown considerable cytotoxicity against both solid tumors and hematological malignancies in vitro and in animal studies. Recently, initial clinical experiences demonstrated the feasibility and efficacy of CIK cell immunotherapy in cancer patients, even at advanced disease stages. Likewise, the clinical application of CIK cells in combination with standard therapeutic procedures revealed synergistic antitumor effects. In this report, we will focus our consideration on CIK cells in the treatment of hematological malignancies. We will give insight into the latest advances and future perspectives and outline the most prominent results obtained in 17 clinical studies. Overall, CIK cells demonstrated a crucial impact on the treatment of patients with hematological malignancies, as evidenced by complete remissions, prolonged survival durations and improved quality of life. However, up to now, the optimal application schedule eventually favoring their integration into clinical practice has still to be developed.
    International Journal of Molecular Sciences 01/2014; 15(8):14632-14648. · 2.46 Impact Factor
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    ABSTRACT: Tumors of the gastrointestinal system represent a significant share of solid tumors worldwide. Despite the advances in diagnosis and treatment, the prognosis of gastrointestinal tumors is still very poor and improved therapies are indispensable. Cytokine-induced killer (CIK) cells are feasible for an immunotherapeutic approach as they are easily available and have an advantageous biologic profile; they are rapidly proliferating and their high cytotoxicity is non-MHC-restricted. We summarize and discuss twenty recent clinical studies applying CIK cells for the treatment of gastric, pancreatic, hepatocellular, and colorectal cancer. Autologous CIK cells were transfused intravenously, intraperitoneally, or via the common hepatic artery. In all studies side effects and toxicity of CIK cell therapy were mild and easily controllable. The combination of CIK cell therapy with conventional adjuvant or palliative therapies was superior to the standard therapy alone, indicating the benefit of CIK cell therapy for cancer patients. Thus, CIK cells represent a promising immunotherapy for the treatment of gastrointestinal tumors. The optimal treatment schedule and ideal combination with conventional therapies should be evaluated in further clinical studies.
    Journal of Immunology Research 01/2014; 2014:897214. · 2.93 Impact Factor
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    V Maevis, U Mey, G Schmidt-Wolf, I G H Schmidt-Wolf
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    ABSTRACT: Hairy cell leukemia (HCL) is part of the low-grade non-Hodgkin lymphoma family and represents approximately 2% of all leukemias. Treatment with splenectomy and interferon-α historically belonged to the first steps of therapeutic options, achieving partial responses/remissions (PR) in most cases with a median survival between 4 and 6 years in the 1980s. The introduction of the purine analogs (PA) pentostatin and cladribine made HCL a well-treatable disease: overall complete response rates (CRR) range from 76 to 98%, with a median disease-free survival (DFS) of 16 years a normal lifespan can be reached and HCL-related deaths are rare. However, insufficient response to PA with poorer prognosis and relapse rates of 30-40% after 5-10 years of follow-up may require alternative strategies. Minimal residual disease can be detected by additional examinations of bone marrow specimens after treatment with PA. The use of immunotherapeutic monoclonal antibodies (mAB) like rituximab as a single agent or in combination with a PA or more recently clinical trials with recombinant immunotoxins (RIT) show promising results to restrict these problems. Recently, the identification of the possible disease-defining BRAF V600E mutation may allow the development of new therapeutic targets.
    Blood Cancer Journal 01/2014; 4:e184. · 1.40 Impact Factor
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    ABSTRACT: Background/Aim: Recent investigations have shown that the Wnt signaling pathway is constitutively activated in multiple myeloma (MM), thereby promoting an exaggerated cell proliferation. Thus, influencing the Wnt pathway might represent a promising target in myeloma treatment. The present study investigated whether a combination of ethacrynic acid (EA) and ciclopirox olamine (CIC) with piceatannol (PIC) would influence the Wnt pathway and viability of human and murine myeloma cell lines by using DiOC6 and propidium iodide (PI) staining, flow cytometry and immunoblotting. The combination of EA with PIC as well as the combination of CIC with PIC had a significant additive effect on the vitality of myeloma cells compared to single-agent application, while healthy cells remained mainly unaffected. Additionally, EA and CIC altered the expression of β-catenin itself and its downstream factors. A combination of Wnt inhibitors could lead to novel treatment options for MM patients.
    Anticancer research 11/2013; 33(11):4719-26. · 1.71 Impact Factor
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    ABSTRACT: Renal impairment is frequent in patients with multiple myeloma and correlates with inferior prognosis. This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospective randomized phase III trial. 827 newly diagnosed myeloma patients in the HOVON-65/GMMG-HD4 trial were randomized to receive 3 cycles of vincristine, adriamycin, dexamethasone (VAD) or bortezomib, adriamycin, dexamethasone (PAD) followed by autologous stem cell transplantation and maintenance with thalidomide 50 mg daily (VAD-arm) or bortezomib 1.3 mg/m2 every 2 weeks (PAD-arm). 746 patients had a baseline-serum creatinine less than 2 mg/dl (Durie-Salmon-stage A) and 81 had 2 mg/dl or higher (stage B). In myeloma patients with base line creatinine ≥2 mg/dl the renal response rate was 63% in the VAD- arm and 81% in the PAD-arm (p=0.31). The overall myeloma response rate was 64% in the VAD-arm versus 89% in the PAD-arm with 13% CR in the VAD arm versus 36% in the PAD arm (p=0.01). Overall survival at 3 years for patients with base line creatinine ≥2 mg/dl was 34% in the VAD-arm versus 74% in the PAD-arm (p<0.001) with a progression-free survival at 3 years of 16% in the VAD-arm versus 48% in the PAD-arm (p=0.004). Overall and progression-free survival in the PAD- arm were similar in patients with base line creatinine ≥2 mg/dl or <2 mg/dl. We conclude that a bortezomib-containing treatment before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in patients with newly diagnosed multiple myeloma. The trial was registered at www.trialregister.nl as NTR213 and at www.controlled-trials.com as ISRCTN 64455289.
    Haematologica 08/2013; · 5.94 Impact Factor
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    ABSTRACT: Interleukin 12 (IL-12), one of the most potent Th1-cytokines, has been used to improve dendritic cells (DC)-based immunotherapy of cancer. However, it failed to achieve clinical response in patients with hepatocellular carcinoma (HCC). In this study, improved conditions of immunotherapy with DC engineered to express IL-12 were studied in murine subcutaneous HCC. Tumour-lysate pulsed DC were transduced with IL-12-encoding adenoviruses or cultivated with recombinant (r)IL-12. DC were injected intratumourally, subcutaneously or intravenously at different stages of tumour-development. Dendritic cell overexpressing IL-12 by adenoviruses showed enhanced expression of costimulatory molecules and stronger priming of HCC-specific effector cells than DC cultured with rIL-12. Intratumoural but not systemic injections of IL-12-DC induced the strongest antitumoural effects reaching complete regressions in 75% of early-staged tumours and in 33% of advanced tumours. Importantly, antitumoural effects could be further enhanced through combination with sorafenib. Analysing the tumour-environment, IL-12-DC increased the levels of Th1-cytokines/chemokines and of CD4(+) -, CD8(+) -T- and NK-cells. Induced immunity was tumour-specific and sustained since all tumour-free animals were protected towards hepatic tumour-cell rechallenge. However, IL-12-DC also enhanced immunosuppressive cytokines, regulatory T cells and even myeloid-derived suppressor cells within the tumours. Induced IL-12-overexpression by adenoviral vectors can effectively immunostimulate DC. Intratumoural but not systemic injection of activated IL-12-DC was crucial for effective tumour regression. The mechanism of this approach seems to be the induction of a sufficient Th1 tumour-environment allowing the recruitment of effector cells rather than the inhibition of tumour immunosuppression. Thus, improved immunotherapy with IL-12-DC represents a promising approach towards HCC.
    Liver international: official journal of the International Association for the Study of the Liver 07/2013; · 3.87 Impact Factor
  • Christiane M Koller, Young Kim, Ingo G H Schmidt-Wolf
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    ABSTRACT: Aim: Advanced renal cancer has still a very poor prognosis. We combined wingless-related integration site (WNT) inhibitors with a bi-functional peptide, as previous research has proven their individual efficacy in cancer therapy. Each targets cancer cells differently. We wanted to determine whether they have an additive effect. Our bi-functional peptide consists of a target domain (LTVSPWY) and a lytic domain (KLAKLAK)2. We used three WNT inhibitors: Ethacrinic acid, ciclopirox olamine, piroctone olamine and combined each with the bi-functional peptide. They were tested on three different renal cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) assay. We demonstrated a synergistic effect of WNT inhibitors with the bi-functional peptide. The vitality of cancer cells was reduced significantly (p<0.05), while healthy cells were mostly unaffected. The combination of WNT inhibitor and the bi-functional peptide may lead to new treatment options as toxic side-effects can be reduced due to the lower doses of agent required.
    Anticancer research 06/2013; 33(6):2435-40. · 1.71 Impact Factor
  • J Khristi, U Mey, J Kirfel, I G H Schmidt-Wolf, I Gütgemann
    Annals of Hematology 04/2013; · 2.87 Impact Factor
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    ABSTRACT: Periodontitis is one of the most prevalent human inflammatory diseases. The major clinical phenotypes of this polymicrobial, biofilm-mediated disease are chronic and aggressive periodontitis, the latter being characterized by a rapid course of destruction that is generally attributed to an altered immune-inflammatory response against periodontal pathogens. Still, the biological basis for the pathophysiological distinction of the two disease categories has not been well documented yet. Type I NKT cells are a lymphocyte subset with important roles in regulating immune responses to either tolerance or immunity, including immune responses against bacterial pathogens. In this study, we delineate the mechanisms of NKT cell activation in periodontal infections. We show an infiltration of type I NKT cells in aggressive, but not chronic, periodontitis lesions in vivo. Murine dendritic cells infected with aggressive periodontitis-associated Aggregatibacter actinomycetemcomitans triggered a type I IFN response followed by type I NKT cell activation. In contrast, infection with Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, did not induce NKT cell activation. This difference could be explained by the absence of a type I IFN response to P. gingivalis infection. We found these IFNs to be critical for NKT cell activation. Our study provides a conceivable biological distinction between the two periodontitis subforms and identifies factors required for the activation of the immune system in response to periodontal bacteria.
    The Journal of Immunology 01/2013; · 5.52 Impact Factor
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    Saineb Al Mansoor, Carsten Ziske, Ingo G H Schmidt-Wolf
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    ABSTRACT: We analysed the typical features of primary small cell carcinoma of the esophagus (SCCE) with emphasis on occurrence, behaviour, outcome and treatment options. This metaanalysis was aimed at collecting and analyzing information from international studies about handling this disease. This seems necessary due to the rarity of this disease. Studies were acquired from electronic databases and reference lists. We finally analysed 313 patient cases from the literature with oesophageal SCC. A data extraction was accomplished referring to 13 evaluable features that are described in the "methods", whereof 7 were analyzed with univariate and multivariate tests. Three hundred thirteen cases were analyzed, 109 patients (35%) had limited stage (LS), whereas 167 (54%) had extensive stage (ES). There is no information about the remaining 35 patients concerning the stage. Univariate and multivariate analysis showed only age (<50 years vs. >50 years, HR 1.024; 95% CI 1.000-1.041, P<0.0001) and disease stage (LS vs. ES, HR 4.884; 95% CI 2.572-9.27, P<0.0001) as significant prognostic factors. There also was a statistically significant difference in survival between those patients who received therapy compared to those who only received best supportive care (11.6 months vs. 0.8 months, HR 0.093, CI 95% 0.053-0.16, P<0.001). In this first multivariate analysis for SCCE we show that SCCE is an aggressive type of tumour with a shorter survival rate compared to its counterpart from the lung. It is demonstrated that only disease stage (limited vs. extensive stage), age (<50 years vs. >50 years) and therapy are independent significant predictors of prognosis.
    German medical science : GMS e-journal 01/2013; 11:Doc12.
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    ABSTRACT: Background:Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients.Methods:We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol).Results:Median age at diagnosis was 59 years (range: 28-77), 32 patients were female. Younger age (Wald=8.9; P=0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald=6.7; P=0.010) were associated with longer overall survival in a multivariate COX regression analysis.Conclusion:This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol.British Journal of Cancer advance online publication, 25 October 2012; doi:10.1038/bjc.2012.476www.bjcancer.com.
    British Journal of Cancer 10/2012; · 5.08 Impact Factor
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    ABSTRACT: PURPOSETo evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. PATIENTS AND METHODS We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. RESULTS: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1(+)) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1(+) was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1(+) AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1(-) t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1(+) again was the sole independent adverse prognostic factor for survival. CONCLUSION Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1(+) MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.
    Journal of Clinical Oncology 09/2012; · 18.04 Impact Factor
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    ABSTRACT: We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.
    Journal of Clinical Oncology 07/2012; 30(24):2946-55. · 18.04 Impact Factor
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    ABSTRACT: New treatment approaches are needed for patients with pancreatic adenocarcinoma. Carcinoembryonic antigen (CEA) is highly expressed on the surface of pancreatic adenocarcinoma cells; we investigated the effects of cytolytic T cells that recognize CEA in a mouse model of pancreatic carcinoma. Immune-competent mice that expressed the CEA transgene (CEAtg) in the intestinal and pulmonary tracts were given intrapancreatic injections of Panc02 CEA(+) cells (express CEA and click beetle luciferase) and tumors were grown for 10 days. Mice were then given single intravenous injections of T cells engineered to express a chimeric antigen receptor (CAR) with high specificity, but moderate affinity, for CEA and a luminescence marker. Injection of the anti-CEA CAR T cells reduced the size of pancreatic tumors to below the limit of detection in all mice and produced long-term tumor eradication in 67% of mice. T cells also eradicated CEA(+) fibrosarcoma cells injected 45 days later. Bioluminescence imaging revealed the accumulation and persistence of the T cells at the tumor site. The efficacy of the T cells did not require lymphodepletion and was not reduced by soluble CEA. Mice developed some noninflammatory infiltrations of CAR(+) T cells in intestine and lung, but there was no evidence of destruction of CEA(+) healthy tissues. Injection of T cells that target CEA can eradicate tumors grown from CEA(+) pancreatic carcinoma cells in the pancreas of CEAtg mice without autoimmune effects.
    Gastroenterology 06/2012; 143(4):1095-1107.e2. · 12.82 Impact Factor

Publication Stats

3k Citations
688.82 Total Impact Points

Institutions

  • 2014
    • Centrum für Integrierte Onkologie
      Köln, North Rhine-Westphalia, Germany
  • 2004–2014
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 2000–2014
    • University of Bonn
      • • Medizinische Klinik und Poliklinik II
      • • Medizinische Klinik und Poliklinik I
      Bonn, North Rhine-Westphalia, Germany
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 2011
    • University of Wuerzburg
      • Department of Internal Medicine II
      Würzburg, Bavaria, Germany
  • 2008–2010
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2005
    • Freie Universität Berlin
      • Department of Hematology
      Berlin, Land Berlin, Germany
  • 2003
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany