RESUMEN
This analysis reports on 72 patients with relapsed or refractory non-Hodgkin lymphoma who were treated with R-DHAP salvage chemotherapy regimen followed by high-dose chemotherapy and stem cell transplantation. The overall remission rate was 58.3%. Median time of follow-up was 28.7 months. Median progression-free survival was 29 months, estimated median overall survival was 37 months. Within a matched pair analysis these results were compared to a group that received DHAP salvage therapy without rituximab showing similar overall response rates and better estimated five-year overall survival of 59.2% versus 43.5%. R-DHAP therapy was shown to be effective and feasible with acceptable toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Citarabina/efectos adversos , Citarabina/uso terapéutico , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Retratamiento , Rituximab/administración & dosificación , Terapia Recuperativa , Resultado del TratamientoRESUMEN
OBJECTIVES: Fusion of dendritic cells (DC) with tumor cells is an approach in immunotherapy combining antigenicity and capacity of antigen presentation to activate T cells for the induction of tumor-specific cytotoxic immunity. Although there have been reports of clinical benefit, response rates have been limited and further improvements are warranted. METHODS: We used murine DC and a novel protocol for an effective fusion of those cells with the murine pancreatic cell line Panc02. RESULTS: We observed 2 events: only moderate in vitro and in vivo cytotoxicity of tumor cell/DC hybrids and a down-regulation of costimulatory molecules on fused cells. Therefore, we transfected tumor cell/DC hybrids with an adenovirus expressing CD154 to improve DC activation and generating antitumor immune response without the need of CD4 T cells. High CD154 expression could be obtained by transfection of DC and Panc02 cells prior fusion. Furthermore, vaccination with CD154-transfected tumor cell/DC hybrid led to a significantly increased induction of cytotoxic T cells in vitro and to an improved antitumoral effect in an orthotopic in vivo mouse model. CONCLUSIONS: CD154-transfected tumor cell/DC hybrids are a promising approach to increase the efficiency of antitumoral response.
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Ligando de CD40/metabolismo , Células Dendríticas/metabolismo , Células Híbridas/metabolismo , Neoplasias Pancreáticas/metabolismo , Animales , Ligando de CD40/genética , Ligando de CD40/inmunología , Línea Celular Tumoral , Células Cultivadas , Citotoxicidad Inmunológica/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Femenino , Citometría de Flujo , Células Híbridas/inmunología , Células Híbridas/trasplante , Inmunoterapia Adoptiva/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Linfocitos T/citología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , TransfecciónRESUMEN
AIM: To investigate the efficacy and safety of cape-citabine plus irinotecan +/- bevacizumab in advanced or metastatic colorectal cancer patients. METHODS: Forty six patients with previously untreated, locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase II trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS: In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients (47% vs 24%), and more patients had colon as the primary tumor site (58.8% vs 48.2%) with fewer patients having sigmoid colon as primary tumor site (5.9% vs 20.7%). Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev: 82% vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates were 70.6% and 75.9%, respectively. No complete responses were observed. The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev, respectively. The median overall survival for CAPIRI was 15 mo (458 d) and for CAPIRI-Bev 24 mo (733 d). These differences were not statistically different. In the CAPIRI-Bev, group, two patients underwent a full secondary tumor resection after treatment, whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION: Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Neoplasias Colorrectales/terapia , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Tolerancia a Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
We randomized 66 elderly patients with AML unfit for conventional chemotherapy to receive GCSF from d6 or from d12 after induction-chemotherapy with cytarabine/idarubicin. There was no difference in duration of neutropenia (17 days vs. 19 days, p=0.67) or rate of complications. Delayed treatment can reduce the administration of G-CSF without adverse consequences.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Leucemia Mieloide Aguda/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Irinotecan is an established therapeutic option in colorectal cancer. An essential side effect of irinotecan treatment is the induction of severe WHO grade 3-4 delayed diarrhea in up to 25% of treated patients. The aim of the study is the prevention of delayed diarrhea with cholestyramine/levofloxacin. PATIENTS AND METHODS: Fifty-one patients with a mean age of 64 years (range: 41-81 years) with metastatic colorectal cancer in second-line treatment were included. A cycle corresponds to 4 applications of irinotecan 250 mg/m2, every 2 weeks, then a break of 2 weeks. RESULTS: After 1 treatment cycle 12% of patients achieved a partial response, 59% had stable disease and 29% progressive disease. Twenty-two patients received a second or more cycles to a total of 379 applications. Forty patients did not develop diarrhea whereas 11 patients had WHO 1-2 diarrhea after at least 1 application of chemotherapy. Diarrhea WHO 3 occurred in only 1 patient (2%) whereas severe diarrhea WHO 4 did not occur. CONCLUSION: The combination of cholestyramine/levofloxacin is a promising option for the prevention of delayed diarrhea caused by irinotecan. This prophylactic regime may help in future to escalate the dose of irinotecan as a monotherapy or in combination protocols.
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Antidiarreicos/uso terapéutico , Camptotecina/análogos & derivados , Resina de Colestiramina/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Diarrea/prevención & control , Levofloxacino , Ofloxacino/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Diarrea/inducido químicamente , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: Dysphagia is the most common disabling symptom in patients with inoperable esophagogastric carcinoma. Self-expanding metal stents are highly effective in the palliation of these patients. METHODS: In 35 patients with inoperable carcinoma of the esophagus or the stomach, with recurrent tumor or complications after transhiatal esophagectomy or gastrectomy or with esophageal stenosis caused by pulmonary cancer, a self-expanding nitinol stent was placed to reduce dysphagia. Dysphagia and WHO performance status were assessed, before and after stent placement. RESULTS: In 35 patients, 39 stents were placed without technical problems. Dysphagia improved significantly. The WHO performance status remained stable. Mean survival of all patients was 11 weeks. Major complications occurred in 3 patients. One patient died of massive tumor bleeding. Minor complications such as stent migration or retrosternal pain occurred in 5 patients. In 2 patients the migrated stent could successfully be placed in the correct position after giving ice-cooled water through the endoscope. Four patients had esophagorespiratory fistulas which were all initially successfully occluded. CONCLUSION: This nitinol stent is highly effective for improving dysphagia in patients with malignant esophagogastric obstruction. We observed no procedure-related complications. Bleeding was the principal major complication. The early intake of cold beverages resulted in stent migration. Recurrent dysphagia due to overgrowth by tumor or nonmalignant tissue remains a problem. Technical improvements are desirable to reduce the overgrowth by nonmalignant tissue.
Asunto(s)
Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Neoplasias Esofágicas/complicaciones , Stents , Neoplasias Gástricas/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Aleaciones , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Estenosis Esofágica/etiología , Estenosis Esofágica/terapia , Esofagectomía , Femenino , Gastrectomía , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Implantación de Prótesis/métodos , Estadísticas no Paramétricas , Stents/efectos adversos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Factores de Tiempo , Organización Mundial de la SaludRESUMEN
Patients treated with monoclonal antibodies and cytokines for cancer receive often co-medication, which may influence treatment efficacy. Therefore, we investigated with a flowcytometric cytotoxicity assay the effect of several immunomodulatory drugs on antibody dependent cellular cytotoxicity (ADCC), interleukin-2 (IL-2) induced cytotoxicity and IL-2-induced-ADCC. We found that dexamethasone markedly inhibited the IL-2 induced cytotoxicity and the IL-2-induced-ADCC. Ondansetron, a 5-HT-3 serotonin receptor antagonist augmented significantly ADCC. Clemastine, a histamine type-2 receptor antagonist augmented the IL-2-induced-ADCC. The TNF antagonist thalidomide suppressed ADCC whereas pentoxifylline proved to be ineffective. Other tested drugs namely ibuprofen and indomethacin, both prostaglandin E2 antagonists, cimetidine a histamine type-2 receptor antagonist, the opioid pethidine, prostaglandin E2 and histamine exerted minor effects or had no influence on the tested parameters. We conclude that glucocorticosteroids should be avoided with monoclonal antibody and cytokine treatment. According to our in vitro data the other drugs tested did not have a negative impact on cellular cytotoxicity and ADCC.
Asunto(s)
Anticuerpos Monoclonales/toxicidad , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Factores Inmunológicos/farmacología , Interleucina-2/toxicidad , Anticuerpos Monoclonales de Origen Murino , Células Cultivadas , Pruebas Inmunológicas de Citotoxicidad , Citometría de Flujo , HumanosRESUMEN
The addition of rituximab to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) has been shown to improve outcome in first-line therapy. However, in patients with relapsed or refractory disease, the value of adding rituximab to salvage chemotherapy is less clearly defined. This study performed a matched-pair analysis of patients with relapsed or refractory DLBCL by comparing the combination of dexamethasone, high-dose cytarabine and cisplatin (DHAP) with rituximab to DHAP alone. Sixty-seven patients with relapsed or refractory DLBCL were collected from two prospective phase II trials from Germany and Italy. Twenty-three patient pairs treated with either DHAP in combination with rituximab or DHAP alone could be analysed after matching for important prognostic factors. The addition of rituximab to the DHAP regimen led to higher complete and similar overall remission rates. However, differences with regard to complete remission rates failed to reach statistical significance, thereby necessitating further evaluation of the role of combined immunochemotherapy in this patient population.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Terapia Recuperativa , Anciano , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Citarabina/administración & dosificación , Citarabina/farmacología , Dexametasona/administración & dosificación , Dexametasona/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , RituximabRESUMEN
We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent. With a median follow-up of 24.9 months, median overall and progression-free survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with rituximab and DHAP proved to be feasible and effective in this patient population.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Femenino , Humanos , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Rituximab , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab , Fluorouracilo/administración & dosificación , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Humanos , Leucovorina/administración & dosificación , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/etiología , Compuestos Organoplatinos/administración & dosificación , Telangiectasia Hemorrágica Hereditaria/complicacionesRESUMEN
HISTORY AND CLINICAL FINDINGS: A 16-year-old previously healthy female patient was admitted with progressive weakness and jaundice. There was no history of journeys to far-away countries. The patient was on oral contraceptives but no other medication, there were no signs of drug abuse. Apart from scleral and skin jaundice all physical findings were normal. INVESTIGATIONS AND DIAGNOSIS: Diagnostic ultrasound showed an enlarged and hyperdense liver. Laboratory tests revealed a markedly increased serum bilirubin, while aminotransferases were only slightly elevated and alkaline phosphatase was unexpectedly low. Prothrombin and antithrombin III levels were low. There was a Coombs-negative hemolytic anemia. Ceruloplasmin was lower than normal. Based on these findings, acute Wilson's disease was suspected. TREATMENT AND COURSE: The patient was immediately transferred to a hepatologic center with transplantation facilities. There, urinary copper excretion and copper concentration in the liver tissue were found to be elevated. Liver histology showed fibrosis but no cirrhosis. Under conservative therapy with trientine liver function recovered, and the patient is well 3 years after the onset of symptoms. CONCLUSION: Acute liver insufficiency should always suggest the possibility of Wilson's disease, particularly when hemolysis is also present.
Asunto(s)
Anemia Hemolítica/etiología , Degeneración Hepatolenticular/diagnóstico , Fallo Hepático Agudo/etiología , Enfermedad Aguda , Adolescente , Anemia Hemolítica/diagnóstico , Biopsia con Aguja , Quelantes/uso terapéutico , Cobre/metabolismo , Cobre/orina , Femenino , Estudios de Seguimiento , Degeneración Hepatolenticular/patología , Humanos , Hígado/metabolismo , Hígado/patología , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/diagnóstico por imagen , Fallo Hepático Agudo/tratamiento farmacológico , Fallo Hepático Agudo/patología , Factores de Tiempo , Resultado del Tratamiento , Trientina/uso terapéutico , UltrasonografíaRESUMEN
BACKGROUND: Modulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored yet. METHODS: Using three different human B cell lymphoma cell lines and primary samples from patients with B cell neoplasms, expression levels of the coxsackie B-adenovirus receptor (CAR) and alpha (v) integrins were analyzed by fluorescence-activated cell sorter (FACS). Adenoviral transduction efficiencies were determined by GFP expression analysis and IL-2 and IL-12 cytokine production was quantified by enzyme-linked immunosorbent (ELISA) assays. Proliferative activities of peripheral blood mononuclear cells (PBMC) stimulated with either cytokine derived from supernatants of transduced lymphoma cells were measured by cell proliferation (MTT) assays. An EuTDA cytotoxicity assay was used to compare cytotoxic activities of IL-2 and/or IL-12 stimulated PBMC against unmodified lymphoma cells. RESULTS: We found that B cell lymphoma cell lines could be transduced with much higher efficiency than primary tumor samples, which appeared to correlate with the expression of CAR. Adenoviral-expressed IL-2 and IL-12 similarly led to dose-dependent increases in proliferation rates of PBMC obtained from healthy donors. IL-2 and/or IL-12 transduced lymphoma cells were co-cultured with PBMC, which were assayed for their cytolytic activity against unmodified lymphoma cells. We found that IL-2 stimulated PBMC elicited a significant anti-tumor effect but not the combined effect of IL-2/IL-12 or IL-12 alone. CONCLUSION: This study demonstrates that the generation of recombinant adenovirus modified lymphoma cell vaccines based on lymphoma cell lines expressing IL-2 and IL-12 cytokine genes is technically feasible, induces increases in proliferation rates and cytotoxic activity of co-cultured PBMC, and warrants further development for the treatment of lymphoma patients in the future.
RESUMEN
Therapeutic vaccination with dendritic cells (DC) can lead to tumor regression in animal models and has shown promising results in the first clinical trials of metastatic renal cell carcinoma and malignant melanoma. In vitro data and results of a clinical phase I/II trial using DC tumor fusions in patients with progressive metastatic renal cell carcinoma are presented here. In addition to toxicity and feasibility, complex immune monitoring was a point of interest. DC precursor cells were obtained from the peripheral blood mononuclear cells (PBMCs) of healthy donors and were fused with either allogeneic (8 patients) or autologous (4 patients) renal tumor cells. In total, 12 patients with progressive metastatic renal cell carcinoma were treated with an average of 2.8 x 10(7) tumor cells fused with 1.8 x 10(7) DC each administered on days 0, 28, and 56 intradermally. Fusion efficacy for the tumor cells used was 14.3% +/- 7.8%. Cell viability was 59.8% +/- 6.8% after fusion and irradiation. We observed no adverse effects and no difference in clinical outcome between the allogeneic and the autologous treatment. Eight patients remained in a progressive disease state and four patients in a stable disease state. T-cell immunity was carefully monitored before, during, and after treatment. Delayed-type hypersensitivity (DTH) reaction using tumor cells was positive after treatment in 7 of 12 patients, 2 of whom were found to have stable disease. An increase in the reactivity against recall antigens was seen in most patients. Interestingly, cytotoxicity of peripheral blood lymphocytes (PBLs) against renal cell carcinoma cells increased during treatment as well as the percentage of interferon-gamma-secreting cells. This effect was significantly enhanced within the group that had stable disease. The lack of adverse effects together with positive immunologic signs justifies further investigation of this novel therapeutic approach. Further studies are necessary to test for clinical effectiveness in patients with tumors, especially those with less advanced disease.
Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Células Renales/terapia , Células Dendríticas/inmunología , Neoplasias Renales/terapia , Adulto , Anciano , Antígenos CD/metabolismo , Vacunas contra el Cáncer/inmunología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Fusión Celular , Citocinas/biosíntesis , Citocinas/sangre , Pruebas Inmunológicas de Citotoxicidad , Células Dendríticas/citología , Técnica del Anticuerpo Fluorescente , Humanos , Isoantígenos/inmunología , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Activación de Linfocitos , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Metástasis de la Neoplasia , Linfocitos T Citotóxicos/inmunología , Resultado del Tratamiento , Células Tumorales CultivadasRESUMEN
In this study we have presented in vitro data and results of a preliminary clinical trial using dendritic cells (DC) in patients with progressive metastatic renal cell carcinoma. DC precursor cells were obtained from peripheral blood mononuclear cells (PBMC). DC were pulsed with autologous tumor cell lysate if available. In total, 15 patients were treated with a median of 3.95 x 10(6) DC administered and ultrasound-guided into a lymph node or into adjacent tissue. Seven patients remained with progressive disease (PD), 7 patients showed stable disease (SD), and one patient displayed a partial response (PR). Most interestingly, the patient who was treated with the highest number of DC (14.4 x 10(6) DC/vaccine) displayed a PR. Delayed-type hypersensitivity (DTH) reaction using autologous tumor lysate was positive in 3 out of 13 patients, including the patient with PR. Two out of 3 patients receiving additional treatment with keyhole limpet hemocyanin (KLH) showed reactivity to KLH after vaccination. CD3+CD4+ and CD3+CD28+ cells as well as the proliferation rate of peripheral blood lymphocytes (PBL) increased significantly in the blood of patients during therapy. In conclusion, our observations confirm the capability of tumor-lysate pulsed autologous DC vaccines to stimulate an immune response in patients with metastatic renal cell carcinoma even in the presence of a large tumor burden. The lack of adverse effects together with immunologic effects support further investigation of this novel therapeutic approach. Further studies are necessary to demonstrate clinical effectiveness in cancer patients, in particular in patients with less advanced disease.