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J W Tervaert

Publications and source records attributed to J W Tervaert.

At least 19 recordsLinked to original sources
PubMed2003

[Treatment of patients with Wegener's granulomatosis or ANCA-associated vasculitis].

Standard therapy of Wegener's granulomatosis is prednisolone in combination with cyclophosphamide. Cyclophosphamide is continued for 15-18 months after diagnosis. During therapy 26% of the patients have severe or life-threatening side effects, mostly infections. Furthermore, there are multiple long-term side effects such as an increased incidence of malignancies, especially bladder carcinoma. During the last 10 years the European vasculitis study group (www.vasculitis.org) organized several randomized clinical trials to determine optimal treatment. Recently, it was demonstrated in one of these trials that in patients with generalized ANCA-associated vasculitis (vasculitis associated with antineutrophil cytoplasmic autoantibodies) withdrawal of cyclophosphamide and substitution by azathioprine after remission did not increase the rate of relapse and was safe. Wegner's granulomatosis is not a fatal disease anymore. Sometimes, however, patients lose their job. Fortunately, this occurs only in a small percentage of patients.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Native and recombinant proteins to analyze auto-antibodies to myeloperoxidase in pauci-immune crescentic glomerulonephritis.

The prevalence of Anti-Neutrophil Cytoplasmic Antibodies (ANCA) directed against myeloperoxidase (MPO) in pauci-immune necrotizing crescentic glomerulonephritis (NCGN) is dependent on the assay(s) used. We investigated the frequency of MPO-ANCA as detected by different assays for MPO-ANCA in a large cohort of patients with biopsy-proven pauci-immune NCGN. Sera from 121 consecutive untreated patients presenting with pauci-immune NCGN were tested for ANCA directed to proteinase-3 (PR3) at diagnosis. PR3-ANCA negative sera were tested by direct ELISA using recombinant or native MPO and by capture ELISA using two different specific monoclonal antibodies directed to MPO and three different antigenic sources. Sera from 80 relevant disease controls were tested to explore the specificity of the different assays. Thirty-eight out of 121 patients (31%) with pauci-immune NCGN did not have PR3-ANCA. Sufficient amounts of serum from 30 of these 38 PR3-ANCA negative patients were available for further testing. Recombinant and native MPO were recognized by similar numbers of sera in a direct ELISA (recombinant MPO: 93%, native MPO: 93%) and a capture ELISA (recombinant MPO: 77-87%, native MPO: 93%). Sera of patients with PR3-ANCA positive pauci-immune NCGN and disease controls were less frequently positive for MPO-ANCA in a capture ELISA (recombinant MPO: 3-7%, native MPO: 6-7%) than in a direct ELISA (recombinant MPO: 25%, native MPO: 13%). Both direct and capture ELISA assays using either native or recombinant MPO are sensitive techniques to detect MPO-ANCA in patients with pauci-immune NCGN. A capture ELISA performs better than a direct ELISA because it combines a higher specificity with a comparable sensitivity. Recombinant MPO is a good alternative for native MPO when used as antigen in a capture ELISA, but not when used in a direct ELISA because of lower specificity in this latter assay.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Renal expression of endothelial and inducible nitric oxide synthase, and formation of peroxynitrite-modified proteins and reactive oxygen species in Wegener's granulomatosis.

To investigate the role of nitric oxide (NO) in glomerular inflammation, the expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was studied in conjunction with inflammatory cell influx, H2O2 production, and the formation of nitrotyrosines in renal biopsies from patients with Wegener's granulomatosis (WG). Renal cryostat sections from patients with WG (n=15) were stained by immunohistochemistry for eNOS, iNOS, endothelial cells (CD31), nitrotyrosines, polymorphonuclear cells (PMNs, CD15), and monocytes/macrophages (CD14, CD68). Production of H2O2 was identified by enzyme cytochemistry using diaminobenzidine. In control tissues, strong staining for eNOS was found in glomerular and interstitial tubular capillaries and cortical vessels. A significant reduction in eNOS expression was found in WG biopsies, which was associated with a reduction in CD31 expression. Expression of iNOS was found in infiltrating inflammatory cells, mainly located in the interstitium. H2O2-producing cells were detected in glomeruli and were abundantly present in the interstitium. Nitrotyrosine-positive cells, however, were almost exclusively found in the interstitium. It is concluded that renal inflammation in WG is associated with the induction of iNOS in inflammatory cells and the formation of nitrotyrosines. Expression of eNOS in glomerular capillaries is lost, most likely due to endothelial cell damage. These results suggest that decreased NO production by endothelial cells, in conjunction with increased NO production by iNOS-positive inflammatory cells, is involved in renal tissue injury in WG.

3,3'-Diaminobenzidine↗
PubMed2001

Are antineutrophil cytoplasmic antibody-associated vasculitides pauci-immune?

The role of ICs in ANCA-associated vasculitides remains controversial. The ANCA-associated vasculitides are described as being pauci-immune. We hypothesize that the absence of ICs is a result of an exaggerated inflammatory response caused by the presence of ANCAs. We present evidence indicating that ICs may play a role in the initiation or relapses of the disease. The nature of the involved antigen(s) is not yet known. Possible candidates are reviewed and include ANCA antigens, AECA antigens, and staphylococcal antigens.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein.

BACKGROUND: Treatment of hypercholesterolaemia with HMG-CoA reductase inhibitors results in an earlier reduction of morbidity and mortality than expected from trials using conventional cholesterol-lowering therapies. Possible explanations for this effect include stimulation of angiogenesis, improvement of endothelial function, plaque stabilisation, inhibition of coagulation and/or thrombocyte aggregation and inhibition of the inflammatory response associated with atherosclerosis. METHODS: We investigated whether statins exert their effects by inhibition of endothelial activation, inflammation and/or monocyte/macrophage activation by measuring plasma levels of soluble cell adhesion molecules, neopterin and C-reactive protein upon treatment with fluvastatin for a period of 12 months in patients with established atherosclerosis and hypercholesterolaemia. RESULTS: Blood samples were taken at baseline and at 3 and 12 months after starting treatment with fluvastatin 80 mg daily. Upon treatment, a reduction of s-ICAM-1 (956.3+/-123.6 vs. 745.4+/-127.4 vs. 674.9+/-70.8 ng/ml, P<0.05) and s-E-selectin (58.6+/-6.7 vs. 47.0+/-6.1 vs. 44.9+/-3.2 ng/ml, P<0.01) was observed. In addition, levels of neopterin decreased, albeit transiently (7.1+/-0.7 vs. 6.0+/-0.5 vs. 6.5+/-0.8 nmol/l, P=0.02), suggesting a reduction in monocyte/macrophage activity. Moreover, we found a decrease in levels of C-reactive protein during follow-up (5.21+/-2.0 vs. 3.18+/-0.7 vs. 1.95+/-0.3 mg/l, P<0.05), compatible with a reduction in inflammatory activity. CONCLUSION: We conclude that statins have a combined beneficial effect on monocyte/macrophage activity, endothelial function and systemic inflammatory activity.

Journal Article↗
PubMed2001

Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers.

UNLABELLED: Sepsis resulting in multiorgan failure and death is still a major problem in intensive care medicine, despite extensive attempts to interfere in the supposed underlying mechanism of a deranged immune system. This is not only due to the persistent lacunae in knowledge about the immune system in sepsis but also due to the lack of sufficient instruments for intervention. Inhibitors of the p38 mitogen-activated protein kinase (p38MAPK) have been used to study the signalling pathway of the immune response. In vitro and animal studies have demonstrated that blocking p38MAPK could mitigate the pro-inflammatory response and improve survival after endotoxaemia. Using an endotoxaemia model in healthy human volunteers we evaluated the attenuation of clinical and cytokine response to endotoxin after inhibition of p38MAPK by an oral dose of RWJ-67657, a pyrindinyl imidazole. We measured the clinical parameters temperature, blood pressure and heart rate. The proinflammatory cytokines tumour necrosis factor-alpha, interleukin-6 and interleukin-8 were measured by ELISA at various points during a 24-h period. Drug toxicity was evaluated by routine clinical and laboratory examinations. After a single dose dose of RWJ-67657 the temperature and blood pressure response remained at the basal level. The inhibition of TNF-alpha, IL-6 and IL-8 response was a dose dependent. With the maximum dosage, reduction in peak serum levels of the proinflammatory cytokines was greater than 90%. There was no drug-related toxicity. INTERPRETATION: We conclude that inhibition of p38MAPK by RWJ-67657 might be a tool to intervene in the deranged immune response in sepsis and other inflammatory diseases.

Adult↗
PubMed2001

Patients with systemic vasculitis have increased levels of autoantibodies against oxidized LDL.

Oxidation of low density lipoprotein (LDL) is considered to play an important role in the development of atherosclerosis and increased levels of autoantibodies against oxidized LDL have been found in patients with various manifestations of atherosclerosis. Patients with vasculitis are prone to the development of atherosclerosis. Since production of radical oxygen species in these patients may result in increased production of oxidized LDL (Ox-LDL), we hypothesized that antibodies against Ox-LDL are elevated during lesion development in vasculitis. Therefore we measured anti Ox-LDL antibodies in 25 patients with ANCA-associated vasculitis and in 42 healthy controls using an ezyme-linked immunosorbent assay (ELISA) in which malondialdehyde modified LDL (MDA-LDL) was coated on microtitre plates. Anti Ox-LDL antibodies were significantly higher in patients as compared to controls (P = 0.0001). Anti Ox-LDL levels were also measured in 11 patients during active disease and in these same patients during complete remission. Anti Ox-LDL levels were significantly higher in patients during active disease than during full remission (P = 0.001). Our results suggest that patients with ANCA-associated vasculitis are more susceptible to oxidation of LDL, which may contribute to accelerated atherosclerosis development.

Adult↗
PubMed2001

Antineutrophil cytoplasmic antibodies to proteinase 3 in Wegener's granulomatosis: epitope analysis using synthetic peptides.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) to proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity nor to functional effects of these antibodies in vitro, suggesting differences in epitope specificity. To define relevant epitopes for PR3-ANCA, sera of WG patients were analyzed on their reactivity to linear peptides of PR3. METHODS: Fifty linear peptides of 15 amino acids in length with an overlap of 10 aa spanning the entire PR3 sequence were synthesized. Sera of 27 WG patients with active disease and 27 age- and sex-matched healthy controls, eight anti-PR3 monoclonal antibodies (mAbs), and a rabbit anti-PR3 serum were tested by enzyme-linked immunosorbent assay for reactivity to PR3 peptides. RESULTS: Rabbit anti-PR3 serum recognized three distinct peptide areas, whereas none of the anti-PR3 mAbs bound PR3 peptides. Sera of both WG patients and healthy controls recognized a restricted number of PR3 peptides. Four of these peptide areas were recognized significantly more strongly by WG sera than by control sera. Sera drawn at the initial presentation of WG mainly recognized these peptides. Two of the recognized peptide areas were located near the active center of PR3. CONCLUSION: A restricted number of epitope areas of PR3 are recognized both by WG patient sera and control sera. Four peptide areas were bound stronger by sera of WG patients at initial presentation than by healthy controls.

Adult↗
PubMed2001

Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.

High-dose corticosteroids in combination with cytotoxic drugs are universally accepted as the initial approach in vasculitides that are associated with anti-neutrophil cytoplasmic antibodies. Cyclophosphamide is the most effective cytotoxic drug and is used in more severe cases. Because cyclophosphamide has more severe short- and long-term side-effects than methotrexate, methotrexate is used in less severe cases. New prospects for the treatment of vasculitis include novel immunosuppressive agents (e.g. mycophenolate, 15-deoxyspergualin, and leflunomide), sequential chemotherapy (e.g. cyclophosphamide followed by azathioprine or cyclophosphamide followed by methotrexate), intravenous immunoglobulin, tumour necrosis factor-alpha directed therapy, anti-lymphocyte directed therapy (e.g. antithymocyte globulin or anti CD52/anti CD4 antibodies), anti-adhesion molecule directed therapy (e.g. anti-CD18 or intercellular adhesion molecule-1 antisense) or immunoablation using high-dose cytotoxic medication with or without stem cell rescue.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Detection of immune deposits in skin lesions of patients with Wegener's granulomatosis.

BACKGROUND: Wegener's granulomatosis (WG) is considered a pauci-immune systemic vasculitis based on the absence of immune deposits in renal biopsies of patients with active disease. In animal models of antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis, immune deposits along the glomerular capillary wall are present at early stages of lesion development. These deposits are degraded rapidly, resulting in "pauci-immune" lesions. OBJECTIVE: To test the hypothesis that immune deposits can also be detected in early lesions of patients with WG, thereby initiating an inflammatory reaction that, in time, is augmented in the presence of ANCA, resulting in pauci-immune lesions later on. METHODS: The presence of immune deposits in skin biopsies taken within 48 hours of lesion development was investigated. Direct immunofluorescence was used to examine 32 skin biopsies for the presence of immune deposits (IgG, IgA, IgM, C3c). When possible, a comparison was made between the immunofluorescence findings in renal and skin biopsies taken at the same time. RESULTS: Four of 11 biopsies taken at initial presentation and four of 21 biopsies taken at the onset of a relapse of WG showed IgG and/or IgA containing immune deposits in the subepidermal blood vessels. All nine renal biopsies showed pauci-immune glomerulonephritis, irrespective of the presence (n=5) or absence (n=4) of immune deposits in the skin biopsy. CONCLUSION: A substantial number of skin biopsies showed immune deposits during active disease. These results could support the hypothesis that immune complexes may trigger vasculitic lesions in WG.

Adult↗
PubMed2000

[Pulmonary hemorrhage with respiratory insufficiency in Henoch- Schoenlein purpura].

A 20-year-old woman presented with abdominal pain, purpura on the extremities, and arthralgia. The diagnosis of Henoch-Schönlein purpura was made based on granular IgA deposits in the vessels in a skin biopsy. Three weeks after onset of these symptoms, she developed glomerulonephritis and diffuse alveolar haemorrhage; she developed respiratory failure and needed mechanical ventilation. She recovered upon treatment with corticosteroids. Diffuse alveolar bleeding has occasionally been reported in adults with Henoch-Schönlein purpura; this is the first report from the Netherlands.

Adult↗
PubMed2000

Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study.

OBJECTIVE: Prediction of relapses in Wegener's granulomatosis (WG) by measuring levels of antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) or myeloperoxidase (MPO) remains a controversial issue. To assess the value of serial quantification of ANCA by indirect immunofluorescence (IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA) for monitoring disease activity in patients with WG, a prospective observational study was conducted in patients with WG attending an outpatient clinic in the Netherlands. METHODS: One hundred patients with WG (85 with PR3-ANCA, 15 with MPO-ANCA) were studied prospectively from 1996 to 1998. Serum samples were obtained and analyzed every 2 months for ANCA levels. Disease activity was prospectively assessed without knowledge of the ANCA levels. RESULTS: Relapses occurred in 37 of 100 patients (37%). Thirty-four (92%) of the 37 patients showed a rise in the level of ANCA preceding their relapse, as detected by ELISA or IIF. The predictive value of an increase in ANCA titers for relapse was 57% (17 of 30) for cytoplasmic/classic ANCA (cANCA; by IIF), 71% (27 of 38) for PR3-ANCA (by ELISA), and 100% (3 of 3) for MPO-ANCA (by ELISA). The predictive value of a rise in ANCA as measured by ELISA or IIF did not substantially improve following concomitant measurement of the IgG3 subclass of PR3-ANCA. Forty-three percent of patients who showed a rise in cANCA (by IIF) and 29% with a rise in PR3-ANCA (by ELISA) did not subsequently experience a relapse. CONCLUSION: Serial measurement of ANCA levels is valuable for the early prediction of relapses in patients with WG.

Adult↗
PubMed2000

Leukocyte activation in sepsis; correlations with disease state and mortality.

OBJECTIVE: The immune response in sepsis shows a bimodal pattern consisting of an early, frequently exaggerated inflammatory response followed by a state of hyporesponsiveness often referred to as the compensatory anti-inflammatory response syndrome (CARS). Insight into the disease state may be helpful in deciding whether to choose immune stimulatory or anti-inflammatory therapy in these patients and may determine clinical outcome. We hypothesized that poor outcome in patients with sepsis is related to the severity of CARS, as reflected in the degree of leukocyte activation. DESIGN: Prospective study. SETTING: Intensive and respiratory care unit at a university hospital. PATIENTS: Twenty consecutive patients with sepsis and 20 healthy age-matched volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Analysis of surface expression of HLA-DR, CD11b, ICAM-1, CD66b, CD63 and CD64 on neutrophils and monocytes by flow cytometry and determination of plasma concentrations of lactoferrin, interleukin 6 and neopterin by ELISA at the time of diagnosis. Patient data were related to those of controls; moreover patient data between survivors and non-survivors were compared. Increased expression of all markers, except HLA-DR, was observed on both neutrophils and monocytes from patients compared to healthy controls. HLA-DR expression on monocytes was significantly decreased in patients with sepsis (p < 0.01). Expression of CD11b and HLE on neutrophils, and ICAM-1 on monocytes, were lower in patients who died compared to those who survived (p < 0.05). CONCLUSION: In sepsis, both neutrophils and monocytes are activated compared to healthy controls. Poor prognosis is associated with a lower expression of activation markers on monocytes and neutrophils, suggesting that poor outcome in these patients may be due to the compensatory anti-inflammatory response.

Adult↗
PubMed2000

Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener's granulomatosis?

The majority of patients with Wegener's granulomatosis (WG) are chronic nasal carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus is associated with an increased risk of developing a relapse of the disease. The mechanism by which this occurs is still unknown. We hypothesized that a cationic protein of S. aureus, staphylococcal acid phosphatase (SAcP), acts as a planted antigen and initiates glomerulonephritis and vasculitis in patients with WG. In order to test the hypothesis that SAcP can act as a planted antigen in WG, we studied the ability of SAcP to bind to human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells. We also studied whether this binding can be prevented by preincubation with an anionic protein, and whether binding of SAcP activates endothelial cells. We also evaluated whether antibodies in sera of patients with WG are able to bind to endothelial cell-bound SAcP. The results show that SAcP can act as a planted antigen by binding to both types of endothelial cells in a concentration-dependent manner. Binding of concentrations as low as 4 microg/ml can be detected on HUVEC within 5 min of incubation. Binding of SAcP to endothelial cells was charge-dependent but did not activate endothelial cells. Finally, endothelial cell-bound SAcP was recognized by sera of patients with WG. The data suggest a possible pathogenic role for SAcP by acting as a planted antigen thereby initiating glomerulonephritis and vasculitis in patients with WG.

Acid Phosphatase↗
PubMed2000

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis.

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Wegener's granulomatosis, microscopic polyangiitis, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis (NCGN) are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against either proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO). This has led some investigators to prefer combining these diseases under the common heading of ANCA-associated vasculitides. However, it is increasingly recognized that there are characteristic differences between patients with anti-PR3 and those with anti-MPO-associated vasculitis. This review focuses on the clinical, histopathologic, and possibly pathophysiologic differences between anti-PR3- and anti-MPO-associated vasculitis. Although there is considerable overlap, the anti-PR3- and anti-MPO-associated vasculitides are each characterized by particular clinical and histopathological findings. Extrarenal organ manifestations and respiratory tract granulomas occur more frequently in patients with anti-PR3 than in those with anti-MPO. Anti-PR3-positive patients with NCGN generally have a more dramatic deterioration of their renal function compared with anti-MPO-positive patients. The term "ANCA-associated vasculitis" is considered as a useful concept in the presence of systemic vasculitis. Likewise, in the presence of vasculitis, the terms "anti-PR3-associated vasculitis" and "anti-MPO-associated vasculitis" are useful concepts.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood.

BACKGROUND: Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular damage during HCMV infection, we investigated the levels of soluble markers during HCMV infection in relationship to EC levels and also preceding the acute rejection episodes. METHODS: Of 46 kidney transplant patients, plasma levels of von Willebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-sel) were analyzed during the course of HCMV infection. RESULTS: Plasma levels of VWF and sVCAM-1 increased twofold during severe HCMV infection. Moreover, the plasma levels of VWF correlated with detectable cytomegalic and noninfected ECs in blood. The kinetics of changes in VWF and ECs (CEC and EC) demonstrated the relationship with HCMV-induced vascular damage. Levels of sICAM-1 and sE-sel in plasma did not significantly change during HCMV infection. Interestingly, the combination of HCMV infection and preceding acute transplant rejection caused the highest increases of VWF and sVCAM-1 plasma levels, reflecting an enhanced susceptibility for endothelial damage at the moment of infection. CONCLUSION: CMV infection is associated with vascular damage, and the vascular damage during CMV infection is enhanced if patients experienced acute rejection before CMV infection.

Acute Disease↗
PubMed2000

CD3 directed bispecific antibodies induce increased lymphocyte-endothelial cell interactions in vitro.

Bispecific antibody (BsMAb) BIS-1 has been developed to redirect the cytolytic activity of cytotoxic T lymphocytes (CTL) to epithelial glycoprotein-2 (EGP-2) expressing tumour cells. Intravenous administration of BIS-1 F(ab')2 to carcinoma patients in a phase I/II clinical trial, caused immunomodulation as demonstrated by a rapid lymphopenia prior to a rise in plasma tumour necrosis factor-alpha and interferon-gamma levels. Yet, no lymphocyte accumulation in the tumour tissue and no anti-tumour effect could be observed. These data suggest a BsMAb-induced lymphocyte adhesion to blood vessel walls and/or generalized redistribution of the lymphocytes into tissues. In this study, we describe the effects of BIS-1 F(ab')2 binding to peripheral blood mononuclear cells (PBMC) on their capacity to interact with resting endothelial cells in vitro. Resting and pre-activated PBMC exhibited a significant increase in adhesive interaction with endothelial cells when preincubated with BIS-1 F(ab')2, followed by an increase in transendothelial migration (tem). Binding of BIS-1 F(ab')2 to PBMC affected the expression of a number of adhesion molecules involved in lymphocyte adhesion/migration. Furthermore, PBMC preincubated with BIS-1 F(ab')2 induced the expression of endothelial cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 during adhesion/tem. These phenomena were related to the CD3 recognizing antibody fragment of the BsMAb and dependent on lymphocyte-endothelial cell contact. Possibly, in patients, the BIS-1 F(ab')2 infusion induced lymphopenia is a result of generalized activation of endothelial cells, leading to the formation of a temporary sink for lymphocytes. This process may distract the lymphocytes from homing to the tumour cells, and hence prevent the occurrence of BIS-1 F(ab')2 - CTL-mediated tumour cell lysis.

Antibodies, Bispecific↗