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Andreas Böhle

Publications and source records attributed to Andreas Böhle.

At least 19 recordsLinked to original sources
PubMed2006

Neutrophil granulocytes are required for effective Bacillus Calmette-Guérin immunotherapy of bladder cancer and orchestrate local immune responses.

The role of polymorphonuclear neutrophil granulocytes (PMN) in antitumoral immune responses displays a striking dichotomy. Under inflammatory conditions, PMN may promote tumor growth and progression. In contrast, especially in the context of therapeutic interventions, PMN can exert important antitumor functions. However, until now, the mechanisms of PMN-mediated activation of tumor immunity are poorly defined. Based on a murine model of Bacillus Calmette-Guérin (BCG) immunotherapy of bladder cancer, we provide evidence for a novel immunoregulatory role of this leukocyte subset. PMN immigrate into the bladder after intravesical BCG instillation and depletion of PMN from tumor-bearing mice completely abrogated antitumor efficacy of BCG. PMN stimulated with BCG in vitro as well as PMN isolated from the urine of BCG-treated patients were a major source of the chemokines interleukin-8, growth-related oncogene-alpha, macrophage inflammatory protein-1 alpha and of the inflammatory cytokine migration inhibitory factor. In vitro, BCG-stimulated PMN indirectly induced T-cell chemotaxis via the accessory function of activated monocytes. In vivo, depletion of PMN from BCG-treated mice significantly impaired CD4(+) T-cell trafficking to the bladder. These data show that PMN direct the migration of effector cells to the bladder and by this means are indispensable for effective tumor immunotherapy. Thus, our findings provide evidence for a novel early immunoregulatory role of these innate immune cells in local antitumor immunity.

Animals↗
PubMed2006

Mycobacteria induce IFN-gamma production in human dendritic cells via triggering of TLR2.

IFN-gamma is of central importance for the induction of robust cell-mediated immunity and for the activation of APC. Recent studies using experimental murine systems have now suggested a fundamental role for APC-derived IFN-gamma during infection with intracellular pathogens. It is currently unknown whether human dendritic cells (DC) can respond to bacterial stimulation with production of IFN-gamma. To test this question, we used human monocyte-derived DC stimulated by Mycobacterium bovis bacillus Calmette-Guérin as a model system. We demonstrate production of IFN-gamma mRNA and protein on the single cell level. IFN-gamma in DC cultures was not simply produced by contaminating lymphocytes because production of DC-IFN-gamma could also be demonstrated in highly purified DC cultures containing virtually no T, B, and NK cells. TLR2 was identified as a key receptor involved in triggering production of DC-IFN-gamma. Interestingly, DC-IFN-gamma seems to participate in an autocrine DC activation loop, and production of DC-IFN-gamma could be enhanced by costimulation of DC with IL-12/IL-15/IL-18. In conclusion, we have demonstrated production of IFN-gamma by human DC on the single cell level, identified TLR2 as a pattern recognition receptor involved in this process, and elucidated some of the functional consequences of autocrine IFN-gamma production by human DC.

Animals↗
PubMed2005

Inhibition of tumor implantation by intravesical gemcitabine in a murine model of superficial bladder cancer.

PURPOSE: We determined if a single intravesical instillation of gemcitabine (2',2'-difluorodeoxycytidine) could prevent the implantation of urothelial cancer cells in the bladder wall of mice, and if 4 weekly treatments could eliminate early implanted bladder cancer in this model. MATERIALS AND METHODS: Tumor implantation and orthotopic bladder tumors were induced in mice by electrocautery of the bladder wall and subsequent instillation of MB49 bladder cancer cells. In the first experiment the tumor cell suspension was left in place for 30 minutes, immediately followed by bladder irrigation and a single intravesical instillation of 250 or 500 microg gemcitabine for 10, 30, 60 or 120 minutes. In the second experiment dwell time was 2 hours, bladders were not irrigated after tumor cell instillation and mice were treated with 4 weekly instillations starting 24 hours after tumor cell implantation. The animals were monitored for side effects and bladder cancer signs, and autopsied at the end of followup. RESULTS: A single intravesical instillation of 500 microg gemcitabine (10 mg/ml) for 30 minutes decreased tumor outgrowth significantly from 90% (control) to 30% (chi-square test p = 0.022). Gemcitabine at 250 microg and prolonged instillations of 500 microg during 60 or 120 minutes were less effective. In the second experiment a short dwell time (30 minutes) was effective at 500 microg doses, resulting in an outgrowth decrease in 89% (control) to 30% of mice, whereas longer instillations (greater than 120 minutes) resulted in significantly reduced tumor outgrowth (11% at 250 microg). The apparent loss of efficacy as a factor of time could not be fully explained. Prolonged bladder distention caused by increased bladder volume due to diuresis may have resulted in trauma and caused enhanced susceptibility to tumor implantation. In the second experiment prolonged instillations (greater than 120 minutes) at 250 microg or higher doses (500 microg) were effective with 11% and 30% outgrowth, respectively. CONCLUSIONS: If given early (within 30 minutes.) after tumor cell seeding, gemcitabine is effective for preventing tumor cell implantation and the resulting tumor outgrowth.

Administration, Intravesical↗
PubMed2004

Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer.

BACKGROUND: Bacillus Calmette Guerin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy. METHODS: Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-gamma ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-alpha and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry. RESULTS: Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-gamma release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1. Immunohistochemical analysis and splenocyte restimulation assay revealed that local and systemic immune responses were triggered by intravesical PstS1-immunotherapy. CONCLUSION: Our results demonstrate profound in vitro activation of human immune cells by recombinant PstS1. In addition, intravesical PstS1 immunotherapy induced strong local and systemic immune responses together with substantial anti-tumor activity in a preclinical mouse model. Thus, we have identified recombinant PstS1 antigen as a potent immunotherapeutic drug for cancer therapy.

Administration, Intravesical↗
PubMed2004

Platelet factor 4 in conjunction with IL-4 directs differentiation of human monocytes into specialized antigen-presenting cells.

Recent evidence suggests that platelets are not only involved in haemostatic processes but also modulate immune responses. As antigen-presenting cells (APC) are of crucial importance for the regulation of immunity, in this study we wanted to define the role of platelet factor 4 (PF-4) as one of the major platelet-derived chemokines on the transition of monocytes into APCs. Our experiments show that within 3 days PF-4 in conjunction with IL-4 induces a rapid differentiation of monocytes into APC. These PFAPC (PF-4/IL-4 differentiated APC) display unique phenotypical and functional characteristics setting them apart from macrophages and conventional dendritic cells. Functional studies revealed that PFAPC preferentially stimulated proliferation of lymphocytes and lytic NK activity while they induced only moderate cytokine responses. Beyond day 3 of differentiation, PFAPC became less immunostimulatory and maintained their capacity to phagocytose particulate material even after LPS-induced maturation. These experiments uncover a previously unknown role for the platelet-derived CXC-chemokine PF-4 in differentiation of human APC. Our data further support the newly discovered function of platelets in immunomodulation and provide new evidence for a rapid transition of monocytes into APC under the influence of inflammatory stimuli.

Antigen-Presenting Cells↗
PubMed2004

Mechanisms of bacillus Calmette-Guerin mediated natural killer cell activation.

PURPOSE: Natural killer (NK) cells are of crucial importance for bacillus Calmette-Guerin (BCG) mediated antitumor effects. We defined the mechanisms of BCG mediated NK cell activation in vitro. MATERIALS AND METHODS: A standard Cr release assay was used to measure the cytotoxicity of BCG activated NK cells. Using the MACS system (Miltenyi Biotec, Bergisch-Gladbach, Germany) we depleted various immune cell subpopulations from BCG stimulated peripheral blood mononuclear cells to phenotype activated NK cells. During the stimulation process anticytokine antibodies and recombinant cytokines were added to define their role in NK cell activation. For costimulation studies peripheral blood mononuclear cells were separated into lymphocytes and monocytes by counterflow-centrifugation (elutriation). Inhibitory NK cell receptor expression on activated NK cells was measured by flow cytometry by antiCD3, antiCD56 and anti-inhibitory NK cell receptor triple staining. RESULTS: The accessory function of monocytes was indispensable for BCG mediated NK cell activation. However, the stimulatory potential of monocytes did not require direct cell-cell contact to NK cells or major histocompatibility complex dependent antigen presentation to T cells. Monocyte derived interleukin (IL)-12 and to a lesser extent interferon (IFN)-alpha were key mediators for stimulating BCG induced NK cell cytotoxicity and IFN-gamma production. In contrast, IL-10 inhibited NK cell cytotoxicity and IL-18 did not show any effect. Exogenous recombinant IFN-alpha and IL-12 enhanced BCG mediated secretion of IFN-gamma and yet BCG induced NK cell cytotoxicity remained unchanged. While the CD158a and CD158b subsets did not have a significant role, NKG2A cells represented the predominant cytolytic subset in BCG activated NK cells. CONCLUSIONS: Following BCG stimulation the monocyte derived TH1 cytokines IL-12 and IFN-alpha activate tumor cytotoxic CD3/CD56/NKG2A NK cells. Our results elucidate NK activating mechanisms that are operative during BCG immunotherapy for bladder cancer and are relevant for an early, innate antimycobacterial immune response.

BCG Vaccine↗
PubMed2004

Histologic tumor growth pattern is significantly associated with disease-related survival in muscle-invasive transitional cell carcinoma of the urinary bladder.

Tumor stage and lymph node status are currently the most established prognostic factors in muscle-invasive bladder cancer. However, there is still a need for new parameters allowing to assess the prognosis more accurately. A recently introduced morphologic classification of tumor growth, which distinguishes three growth patterns (nodular, trabecular, and infiltrative type), was retrospectively applied to a collective of 153 muscle-invasive bladder carcinomas in order to examine its prognostic relevance. Nodular pattern was found in 34 cases (22%), trabecular pattern in 97 cases (63%) and infiltrative pattern in 22 cases (14%) as the dominant type of tumor growth. The majority of cases (54%) displayed more than one tumor growth pattern. A two-tiered classification considering the worst type of tumor growth (non-infiltrative or infiltrative type) yielded 74 non-infiltrative tumors (55%) and 69 infiltrative tumors (45%). The former group was associated with a significantly better disease-related survival than the latter (p=0.007 by univariate Cox regression analysis). Moreover, the two-tiered classification was identified, besides tumor stage (p=0.036) and lymph node status (p=0.0001), as an independent predictor of disease-related survival in a multivariate analysis (p=0.029). In conclusion, our data suggest that the morphologic pattern of tumor growth is significantly associated with the clinical course of advanced transitional cell carcinomas of the bladder. The tumor growth classification proposed here may serve as an additional tool to predict the prognosis of patients undergoing radical cystectomy for bladder cancer.

Aged↗
PubMed2003

Antisense treatment against Ki-67 mRNA inhibits proliferation and tumor growth in vitro and in vivo.

The Ki-67 protein is tightly regulated and depends on the proliferative status of a cell. It is present in the nuclei of proliferating cells but absent in resting cells. Since transformation of malignant cells is frequently associated with high cell proliferation and since proliferation is tightly associated with the Ki-67 protein labeling index, this antigen may represent a potential target for cancer therapy. In the present study we determined the ability of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) targeted against Ki-67 mRNA to inhibit tumor cell proliferation specifically in cell culture, in multicellular 3-dimensional spheroids (MCS) and in subcutaneous murine tumor models. Antisense treatment of 1 myeloid and different epithelial tumor cell lines in suspension and monolayer culture, respectively, resulted in specific reduction of Ki-67 mRNA and protein, inhibition of proliferation and increased apoptotic cell death. Multicellular human bladder carcinoma spheroids lost their 3-dimensional structure and underwent cell death after incubation with antisense oligonucleotides. The growth of subcutaneous syngeneic prostatic (p = 0.05) and transitional cell tumors (p = 0.001) in immunocompetent mice was significantly inhibited in antisense-treated animals. From these findings we conclude that antisense inhibition of Ki-67 protein expression may be a rational approach in anticancer therapy.

Adenocarcinoma↗
PubMed2003

Antisense oligonucleotide therapy for urologic tumors.

Modulation of gene expression using antisense oligonucleotides has advanced from the laboratory to the clinic. Numerous companies can, at least partially, attribute their success to the development of antisense techniques, and one antisense drug is currently on the market. Antisense compounds have been used in clinical trials that included patients with urologic tumors, mostly directed at proliferation- or apoptosis-related targets. Furthermore, therapeutic inhibition of many new identified genes is being investigated in preclinical tests. This review provides a contemporary overview of current preclinical and clinical antisense oligonucleotide concepts for the treatment of urologic tumors.

Animals↗
PubMed2003

Prognostic value of MCM2 immunoreactivity in stage T1 transitional cell carcinoma of the bladder.

OBJECTIVE: Due to the heterogeneous biologic behavior of stage T1 bladder carcinomas, there is a need for new markers allowing to assess the prognosis more accurately. To our knowledge, there are no reports on studies investigating minichromosome maintenance protein 2 (MCM2) expression in bladder carcinomas. Thus, we investigated the prognostic value of MCM2 immunoreactivity in stage T1 bladder tumors. METHODS: Fifty-four tumors were analyzed using Biochip microarrays. Also p53 and Ki67 antigen expression were examined. Immunohistochemical scores were compared with the clinical outcome. RESULTS: During a median follow-up of 43 months, tumor recurrence was registered in 43 and progression to stage T2 in 19 patients. Kaplan-Meier curves demonstrated that high-level MCM2 expression was significantly associated with early tumor recurrence when using a cutoff of 60% (p=0.0035 by log-rank test), and with early tumor progression when using a cutoff of 20% (p=0.0454). There was no relationship (p=0.604) between MCM2 and p53, but a tendentious relationship (p=0.082) between MCM2 and Ki67 antigen expression. MCM2 (p=0.006), Ki67 antigen (p=0.035) and p53 expression (p=0.049) as well as tumor grade (p=0.026) and age (p=0.025) were found significantly associated with recurrence-free survival by univariate Cox regression analysis, among which only Ki67 antigen expression (p=0.015) and age (p=0.019) proved to be of independent predictive value by multivariate analysis. Concerning tumor progression, MCM2 expression was identified as the only predictive parameter by log-rank test, but it was not of independent predictive value by multivariate analysis (p=0.101). CONCLUSION: Our data suggest that MCM2 expression may bear some prognostic relevance in stage T1 bladder carcinomas.

Adult↗
PubMed2003

Primitive neuroectodermal tumor (PNET) of the urinary bladder.

We report on the clinical, morphologic, immunohistochemical, ultrastructural, and molecular cytogenetic features of a primitive neuroectodermal tumor (PNET) primarily arising in the urinary bladder. An 81-year-old man presented with lymphedema of the lower extremities, fatigue, and urge incontinence. Radiographically, a tumor filling the entire cavity of the urinary bladder and extending into the pelvic and retroperitoneal tissue was noted. Histology of tumor biopsies showed a highly cellular, focally necrotic small round-cell tumor with numerous mitoses and occasional rosette-like structures. The tumor cells displayed significant immunoreactivity for neuron-specific enolase (NSE) and the MIC2 gene product (CD99). Dense-core granules were detectable by electron microscopy. A molecular cytogenetic analysis using comparative genomic hybridization (CGH) revealed gains of the chromosomes 3p, 6, 8q, 12, 17q, and 21q. The patient died two weeks after diagnosis. To the best of our knowledge, this is the fifth reported case of a PNET of the urinary bladder, and the first that includes a molecular cytogenetic analysis based on CGH.

12E7 Antigen↗
PubMed2003

Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer.

PURPOSE: Of all medical disciplines it is exclusively in urology in which immunotherapy for cancer has an established position today with intravesical bacillus Calmette-Guerin (BCG) against superficial bladder carcinoma recurrences. BCG is regarded as the most successful immunotherapy to date. However, the mode of action has not yet been fully elucidated. We provide a thorough overview of this complex field of research. MATERIALS AND METHODS: Rather than simply reporting all experimental data available for better understanding the involved immune mechanisms, we chose to provide comprehensively only information supported by several independent pathways of evidence. RESULTS: Major findings made during the last few years include systematic analyses of patient material, detailed in vitro studies and investigations in animal models, which have led to a substantially greater understanding of the mechanisms involved. CONCLUSIONS: The efficacy of BCG is based on a complex and long lasting local immune activation. The bladder as a confined compartment, in which high local concentrations of the immunotherapy agent and effective recruitment of immune cells can be achieved, serves as an ideal target organ for this type of immunotherapy approach.

Adjuvants, Immunologic↗
PubMed2003

Stimulation of neutrophil granulocytes with Mycobacterium bovis bacillus Calmette-Guérin induces changes in phenotype and gene expression and inhibits spontaneous apoptosis.

Polymorphonuclear neutrophil granulocytes (PMN) have been implicated in the early inflammatory response against mycobacteria besides monocytes/macrophages. Yet, little is known about the interaction of mycobacteria with PMN. We investigated the potential of Mycobacterium bovis bacillus Calmette-Guérin (BCG) to stimulate and influence PMN phenotype, gene expression profile and spontaneous apoptosis. Flow cytometric analyses revealed an upregulation of the function-associated molecules Fc gamma receptor III (Fc gamma R III) and II (CD16 and CD32) as well as MAC-1 (CD11b and CD18) on BCG-stimulated PMN. As determined by cDNA microarrays and multiplex reverse transcriptase PCR, stimulation with BCG alters the expression of various genes for proinflammatory cytokines/chemokines or receptors in PMN. We detected an upregulation or de novo synthesis of interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-8, macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, GRO-alpha, transforming growth factor beta, MCP-1, IL-2 receptor gamma (IL-2R gamma), IL-10R alpha, and IL-6R. Genes for IL-9, IL-12 alpha, IL-15, IL-5R alpha, and IL-13R alpha(1) were found to be downregulated or switched off. Furthermore, Giemsa and annexin V-propidium iodide double staining demonstrated an inhibition of spontaneous PMN apoptosis following BCG stimulation. Changes in phenotype and inhibition of apoptosis did not depend on direct mycobacterial stimulation alone, but were a result of an autocrine-paracrine stimulation mechanism. Our findings support the hypothesis that PMN become activated at the site of mycobacterial infections and that this activation might set the stage for a subsequent antimycobacterial immune response.

Antigens, CD↗
PubMed2003

Numerical aberrations of chromosome 17 and the 9p21 locus are independent predictors of tumor recurrence in non-invasive transitional cell carcinoma of the urinary bladder.

Since the majority of patients with non-invasive (stage pTa) bladder carcinoma experience tumor recurrence, the identification of prognostic markers for assessing the biologic behavior of tumors is of high clinical interest. In this retrospective study, we investigated the prognostic value of numerical aberrations of chromosomes 3, 7, 17 and of the 9p21 gene locus in 71 pTa bladder carcinomas using the UroVysion test. This recently developed multi-probe fluorescence in situ hybridization (FISH) test, which simultaneously stains the 9p21 locus and the centromer regions of chromosomes 3, 7 and 17, was applied on paraffin sections from formalin-fixed tumor specimens. All tumors were evaluated for twelve different criteria, among which were: polysomy 3, 7 or 17 in > or =10% of tumor cells, pentasomy or higher polysomy 3, 7 or 17 in > or =1 tumor cell, and loss of both 9p21 alleles in > or =10% of tumor cells. The latter parameter was the most frequent chromosomal aberration (detected in 83% of the tumors), while polysomies 3, 7 and 17 were registered in 27, 13 and 12% of the cases, respectively. Most of the parameters were found at higher frequencies in G3 tumors compared to G1 or G2 tumors. None of the parameters correlated with progression-free survival, but polysomy 3 (p=0.029), polysomy of at least one of the chromosomes 3, 7 or 17 (p=0.032), pentasomy/higher polysomy 17 (p=0.007), and loss of 9p21 (p=0.026), correlated significantly with recurrence-free survival. Of these, pentasomy/higher polysomy 17 (p=0.015) and loss of 9p21 (p=0.036) were identified as independent predictors of tumor recurrence in a multivariate Cox regression analysis that also included tumor grade. In conclusion, we suggest that evaluation of numerical aberrations of chromosome 17 and the 9p21 locus may represent a useful tool to assess tumor recurrence of pTa bladder carcinomas more accurately.

Adult↗
PubMed2002

HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications.

The HER2 (c-erbB-2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti-HER2-directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle-invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin-embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle-invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)-approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high-grade carcinomas than in low-grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan-Meier curves showed a significantly worse disease-related survival (p = 0.034) in patients with HER2-overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle-invasive bladder carcinomas. Because many of these patients harbor HER2-overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.

Adult↗
PubMed2002

The role of LFA-1 in the lysis of bladder cancer cells by bacillus Calmette-Guérin and interleukin 2-activated killer cells.

Activated cytotoxic effector cells such as bacillus Calmette-Guérin (BCG)-activated killer (BAK) and lymphokine-activated killer (LAK) cells are thought to mediate the antitumor effects in the immunotherapy of superficial bladder cancer with BCG. We investigated the role of the leukocyte-function-antigen-1 and its two subunits CD11a and CD18 in the lysis of bladder tumor cells by both effector cell populations. We used flow cytometry to measure CD11a and CD18 expression on BAK and LAK cells. The involvement of both surface molecules in the lysis of bladder tumor cells was determined by phase contrast microscopy and a set of radioactive-release assays using specific inhibitory antibodies. BAK and LAK cells expressed more CD11a and CD18 on their surfaces than unstimulated peripheral blood mononuclear cells. Effector-target cell adhesion was a prerequisite for the cell-mediated cytotoxicity of BAK and LAK cells against bladder tumor targets. Cytotoxicity of both BAK and LAK cells was inhibited by a combination of anti-CD11a and -CD18 monoclonal antibodies. Our study gives further insight into the complex interactions of the adhesion molecules of activated immune cells and their respective tumor targets and might help to increase our knowledge of the molecular mechanisms of BCG-immunotherapy.

CD11a Antigen↗
PubMed2002

Immune gene therapy in urology.

Effective treatments are needed urgently for metastatic disease in bladder, prostate, and renal cell cancer. In the past few years, several new approaches for treating these conditions have been proposed, including gene therapy. A number of different strategies have been developed to accomplish urologic cancer gene therapy. Genetic immunomodulation strategies attempt to activate immune defense mechanisms against tumor cells by transfer of tumor antigens, cytokine genes, or strongly immunogenic cell surface molecules. In this review, we illustrate the recent developments in immune gene therapy.

Carcinoma, Renal Cell↗