Abstract:
:Antibody-dependent cellular cytotoxicity (ADCC) is considered to be the major mechanism through which tumour cells, upon treatment with anti-tumour MAbs, are eliminated in vivo. However, the relative importance of various parameters that influence the efficacy of ADCC is unclear. Here we present in vitro data on the impact of MAb affinity and antigen density on ADCC, as obtained by comparison of two MAbs against the tumour-associated antigen Ep-CAM. The low-affinity MAb 17-1A (Ka = 5 x 10(7)M(-1)) currently used for therapy, and the high-affinity MAb 323/A3 (Ka = 2 x 10(9) M(-1)), were compared in ADCC experiments against murine and human tumour target cells transfected with the Ep-CAM cDNA under the control of an inducible promoter to enable regulation of the target antigen expression levels. Data obtained from these studies revealed that the high-affinity MAb, in contrast to the low-affinity MAb, could mediate killing of tumour cells with low antigen expression levels. Even at comparable MAb-binding levels, ADCC mediated by the high-affinity MAb was more effective. The kinetics of ADCC was also found to be determined by the level of antigen expression, and by the affinity and the concentration of the MAb used. The efficacy of ADCC with both low- and high-affinity MAbs further depended on adhesive interactions between effector and target cells mediated by CD18. However, at every given MAb concentration these interactions were of less importance for the high-affinity MAb than for the low-affinity MAb. As heterogeneity of a target antigen expression is a common feature of all tumours, and some tumour cells express very low levels of the antigen, the use of high-affinity MAbs in immunotherapy may significantly improve the clinical results obtained to the present date in the treatment of minimal residual disease.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Velders MP,van Rhijn CM,Oskam E,Fleuren GJ,Warnaar SO,Litvinov SVdoi
10.1038/bjc.1998.518subject
Has Abstractpub_date
1998-08-01 00:00:00pages
478-83issue
4eissn
0007-0920issn
1532-1827journal_volume
78pub_type
杂志文章abstract::Increasingly, reverse transcriptase polymerase chain reaction (RT-PCR) is used to detect clinically significant tumour cells in blood or bone marrow. This may result in a redefinition of disease-free and clinical relapse. However, its clinical utility may be limited by lack of automation or reproducibility. Recent stu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600014
更新日期:2002-01-07 00:00:00
abstract::Data collected from lung cancer patients attending the Victoria Clinic of the British Columbia Cancer Agency are used to investigate how resources are rationed in the treatment of non-small-cell lung cancer (NSCLC). An ordered logit model is estimated to analyse empirically the relationship between treatment selection...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.136
更新日期:1996-03-01 00:00:00
abstract::Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.196
更新日期:1994-06-01 00:00:00
abstract::Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test is currently of sufficient sensitivity or sp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603188
更新日期:2006-06-19 00:00:00
abstract::The association between breast and endometrial cancer was investigated in a cohort consisting of 60,065 subjects (99% of all women in whom a first breast cancer was diagnosed in Sweden in 1960-63 and 1968-81). Complete follow-up until 1981 revealed a total of 260 endometrial cancers, as against an expected number of 1...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.16
更新日期:1987-01-01 00:00:00
abstract::C57BL mice were given local irradiation to 2 cm2 of the lower abdomen in the dose range 16--24 Gy. There were some early deaths, but mice dying between 50--240 days predominantly developed invasive adenocarcinomas of the intestine. When the radiosensitizer misonidazole was given in a single dose shortly before irradia...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.240
更新日期:1978-10-01 00:00:00
abstract::An enzyme activity with the characteristics of reverse transcriptase was detected in marrow from patients with leukaemia in relapse and in firm haematological remission. The endogenous enzyme activities increased following culture, and in remission patients the enzyme activities reached levels equal to or exceeding th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.95
更新日期:1974-06-01 00:00:00
abstract::A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non-...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1995.255
更新日期:1995-06-01 00:00:00
abstract::Combretastatin-A4 phosphate (cis-CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1653
更新日期:2001-03-23 00:00:00
abstract::Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min i.v. infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1-5) at one of nine dose levels: 24, 48, ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6690232
更新日期:1999-03-01 00:00:00
abstract::The ten most frequently reported pretreatment symptoms on the Rotterdam Symptom Checklist, which was completed by more than 650 patients entering two MRC Lung Cancer Working Party multicentre randomised trials, included general symptoms (tiredness, lack of appetite) and psychological distress (worry, anxiety) in addit...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.124
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:The interaction between human prostate cancer (PCa) cells and bone marrow (BM) endothelium follows a rolling-and-adhesion cascade mediated by E-selectin ligand (ESL): E-selectin. This adhesion is enabled by elevated expression of α-1,3-fucosyltransferases (FTs), enzymes responsible for ESL-mediated bone meta...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.690
更新日期:2013-12-10 00:00:00
abstract::The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized tri...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.bjc.6690426
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.228
更新日期:2012-07-24 00:00:00
abstract::A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.93
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:We previously reported that chaetocin has potent and selective anti-myeloma activity attributable to reactive oxygen species (ROS) induction imposed by inhibition of the redox enzyme thioredoxin reductase; we now detail its effects in solid tumours. METHODS:Cellular assays, transcriptional profiling and the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.522
更新日期:2012-01-17 00:00:00
abstract:BACKGROUND:We evaluated systemic immune-inflammation index (SII) and its association with patient outcome in germ-cell tumours (GCTs). METHODS:Two independent cohorts of patients were analysed; the discovery set (n=171) from a single institution and the validation set (n=181) previously included in a study evaluating ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.460
更新日期:2018-03-20 00:00:00
abstract::Increased fibre intake has been shown to reduce serum oestrogen concentrations. We hypothesized that fibre exerts this effect by decreasing the time available for reabsorption of oestrogens in the colon. We tested this in volunteers by measuring changes in serum oestrogen levels in response to manipulation of intestin...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/bjc.1997.397
更新日期:1997-01-01 00:00:00
abstract::Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies e...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1054/bjoc.2001.2040
更新日期:2001-09-28 00:00:00
abstract:BACKGROUND:Isolated groups, such as first generation non-Western immigrants, are at risk for suboptimal utilisation of the health care system resulting in a worse outcome. METHODS:From 1989 to 2007, all patients with stomach cancer were selected from the Comprehensive Cancer Centre North-East cancer registry. Associat...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.64
更新日期:2011-03-29 00:00:00
abstract::Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602535
更新日期:2005-04-25 00:00:00
abstract:BACKGROUND:First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS:This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2017.252
更新日期:2017-09-05 00:00:00
abstract:BACKGROUND:Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP). METHODS:This Canadian population-based case-control study (2001-2012) included 854 invasive cases/2139 controls aged ⩾40 years who...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.400
更新日期:2017-01-17 00:00:00
abstract:BACKGROUND:Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.433
更新日期:2018-02-20 00:00:00
abstract:BACKGROUND:Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605104
更新日期:2009-07-07 00:00:00
abstract::The normal-lymphocyte-transfer test has been advocated as a method of assessing the immuno-competence of lymphocytes from patients with breast and large-bowel cancer. Evidence is presented in this paper that the methodology is subject to many uncontrollable errors, that the reaction is the result of multiple factors, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.219
更新日期:1978-09-01 00:00:00
abstract::Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence in men with HIV infection. We performed a matched case-control study comparing outcomes in HIV-positive men and the general population with GCT, using three age and stage matched controls for each case. There was no differ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601762
更新日期:2004-04-19 00:00:00
abstract::The level of Gross cell-surface antigen (GCSAa) expression at the surface of murine retrovirus-infected fibroblasts was determined by quantitative absorption of the anti-GCSAa activity of a serum produced in syngeneic W/Fu rats immunized against (C58NT)D lymphoma, and tested in a cytotoxicity assay against E male G2 l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.97
更新日期:1981-05-01 00:00:00
abstract::Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990-2003. We compared incidence rates among new ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605024
更新日期:2009-05-05 00:00:00
abstract::Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.174
更新日期:1980-06-01 00:00:00