Abstract:
:ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two Phase I/II trials in relapsed small cell lung cancer and metastatic breast cancer. To improve the effector functions of the antibody, increase its half-life in circulation, and avoid the human antimouse antibody response, two chimeric and several humanized antibodies were constructed for evaluation. The chimeric IgG1 is more potent than the murine IgG3 in tumor cell lysis via activation of human peripheral mononuclear cells (10-fold), but somewhat less effective in complement-dependent lysis (2-3 fold). The chimeric IgG3 is slightly less potent than the IgG1. A humanized IgG1 was constructed by combining the complementarity-determining regions of the ABL 364 antibody with human framework and constant regions. Several additional variants were subsequently constructed to improve the binding affinity and increase expression of the antibody. Two of the variants, designated I and K, differ by a single amino acid at position 75 of the heavy chain. Both variants have affinity within 2-fold of the chimeric IgG1 antibody and retain the cytolytic activities toward tumor cell lines. However, it was possible to express variant K at a significantly higher level (5- 10-fold) than variant I. Pharmacokinetics of the humanized ABL 364 antibody variant K was compared with that of the parent murine antibody in rhesus monkeys. It was shown that the terminal half-life of the humanized antibody in rhesus monkeys is 14-20 days, with a mean of 16.3 days, while that of the parent murine antibody is only 1.9 days.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Co MS,Baker J,Bednarik K,Janzek E,Neruda W,Mayer P,Plot R,Stumper B,Vasquez M,Queen C,Loibner Hsubject
Has Abstractpub_date
1996-03-01 00:00:00pages
1118-25issue
5eissn
0008-5472issn
1538-7445journal_volume
56pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Inbred rodent strains with differing sensitivity to experimental tumor induction provide model systems for the detection of genes that either are responsible for cancer predisposition or modify the process of carcinogenesis. Rats of the inbred BD strains differ in their susceptibility to the induction of neural tumors...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
abstract::The reactivity of normal and tumor host lymphocytes incubated with normal serum or with serum or malignant ascites fluid from tumor hosts was measured by the ability of the lymphocytes to synthesize ornithine decarboxylase after phytohemagglutinin stimulation. Each of three tumors tested (a solid fibrosarcoma, an asci...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract::To elucidate the role of the recently identified FHIT gene, located at 3p14.2 in human brain tumor carcinogenesis, a total of 259 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D3S1313, D3S1234, D3S1300, and D3S1481. In primary brain tumors, LOH was detected at a frequency of 8.4% (n = 21...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study w...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-3466
更新日期:2005-05-01 00:00:00
abstract::Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pol eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1862
更新日期:2006-01-01 00:00:00
abstract::Cancer patients showing local failure after radiation treatment have increased probability for developing metastatic disease. The mechanisms behind this observation have not been identified. In the present work, metastatic spread after inadequate radiation therapy was studied by using R-18 human melanoma xenografts as...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2658
更新日期:2004-01-01 00:00:00
abstract::Cyclooxygenase, involved in tumor growth and angiogenesis, converts arachidonic acid to prostaglandin (PG)H(2), which is immediately converted to bioactive prostanoids including PGE(2), PGD(2), thromboxane (TX)A(2) and PGI(2). To test the hypothesis that changes in the prostanoid profile alter cancer growth, we transd...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Synovial sarcoma is a soft tissue malignancy characterized by the fusion of SS18 to either SSX1, SSX2, or SSX4 genes. SS18 and SSX are transcriptional cofactors involved in activation and repression of gene transcription, respectively. SS18 interacts with SWI/SNF, whereas SSX associates with the polycomb chromatin rem...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0092
更新日期:2008-06-01 00:00:00
abstract::A purse-string suture was put into the rat's cecum to form a "diverticulum." When the thread cut this stitch, the resultant extensive necrotic zone healed for a long time. The presence of a foreign body (ligature) provided a permanent source of injury to the cecal mucosa. The lesions caused an increase in [3H]thymidin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the sper...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-02-01 00:00:00
abstract::The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Cyclin A is an S- and G2-M-phase regulatory protein, and its abnormal expression has been implicated in cellular transformation. This work was undertaken to investigate the frequency of cyclin A overexpression and the correlated clinical outcome in human hepatocellular carcinoma (HCC). Herein, 12 of 31 (39%) patients ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::Aldophosphamide (NSC 254), a putative key metabolite of cyclophosphamide, has now been isolated as a cyanohydrin derivative from an incubation mixture of cyclophosphamide with mouse liver microsomes in vitro and from the plasma of a cyclophosphamide-treated patient. The cyanohydrin has been shown to be identical with ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-08-01 00:00:00
abstract::The data of nine monolayer cultures, 48 multicellular spheroids, and 19 s.c. xenografts of LoVo cells were fitted, on an individual basis, by exponential and Gompertzian equations, respectively. The mean growth parameters alpha 0 (initial growth rate) and beta (retardation factor) of the three experimental systems pre...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Mitomycin C (MMC), a known cytotoxic agent, requires cellular enzyme-mediated activation for effective antitumor activity. To study the bioreductive enzymes responsible for MMC activation in tumor cells, we examined the enzyme activities of DT-diaphorase (DTD) and NADPH:cytochrome P-450 reductase in 13 colon and gastr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-06-15 00:00:00
abstract::Upon MYC inactivation, tumors variously undergo proliferative arrest, cellular differentiation, and apoptosis and in some cases, apparently permanently revoking tumorigenesis. In liver tumor cells, we recently showed that MYC inactivation uncovers stem cell properties and triggers differentiation, but in this case, th...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-05-1172
更新日期:2005-06-01 00:00:00
abstract::Vascular endothelial growth factor D has recently been linked to the control of lymphangiogenesis and lymphatic metastasis. The molecular determinants regulating vegf-D gene transcription, however, have not yet been identified. After isolation of 2 kb of 5'-flanking DNA of the human vegf-D gene, we identified a novel,...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5136
更新日期:2008-01-15 00:00:00
abstract::Microsomal epoxide hydrolase (mEH) is involved in the metabolism of tobacco-derived carcinogens. Polymorphisms in exons 3 and 4 of the EPHX gene have been reported to be associated with variations in mEH activity. We examined whether the predicted mEH activity modified the lung cancer risk among 150 cases and 172 cont...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::In order to evaluate geographical differences in the liver pathology of ducks infected with duck hepatitis B virus (DHBV), ducks in Chiba and Shimane, Japan, and Shanghai, China, were investigated. The numbers (DHBV positive/negative) and the maximum age of the ducks examined were 18/10 at 19 mo, 15/1 at 3 yr 4 mo, an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Primary solid tumors were mechanically and/or enzymatically disassociated, and the resulting suspensions of single cells and small clumps of cells were seeded onto three different substrates, i.e., tissue culture plastic, rat smooth muscle cells (SMCs), and SMC-derived extracellular matrix. Tests of the relative effec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::This report describes and presents some preliminary results from a prospective clinical investigation to determine the ablative effect of thiotepa (N,N',N''-triethylene phosphoramide) on superficial low-stage bladder cancer and the effectiveness of this agent in the prevention of recurrent or new tumors. In the small ...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1977-08-01 00:00:00
abstract::Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high con...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1990-10-15 00:00:00
abstract::Murine monoclonal antibodies of the immunoglobulin G2a isotype interact with human effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC) directed against malignant cells which express antigens recognized by these antibodies. gamma-Interferon enhances these effects in vitro. In a Phase I trial of mu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Friend erythroleukemia cells can be induced to undergo erythroid differentiation by a variety of unrelated compounds. The fact that sodium butyrate causes reversible alterations in growth, morphology, and biochemistry in many cell systems prompted us to reexamine its pattern of induction of differentiation and to comp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-01-15 00:00:00
abstract::After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::The expression of defects in the control of cellular differentiation is thought to be of etiological significance in the early stages of carcinogenesis. This possibility is supported by a variety of experimental studies including those that have established that metaplastic changes in cells can represent preneoplastic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impact...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1231
更新日期:2020-11-15 00:00:00
abstract::Carcinomas of the exocrine pancreas are poorly understood and have a poor prognosis because of their highly malignant nature. Using two human pancreatic cancer cell lines, AsPc-1 and Capan-2, we have investigated avenues that might be useful in targeting the delivery of antineoplastic agents to such cancers. Qualitati...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Microarray gene expression profiling is a powerful tool for generating molecular cancer classifications. However, elucidating biological insights from these large data sets has been challenging. Previously, we identified a gene expression-based classification of primary uveal melanomas that accurately predicts metasta...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4196
更新日期:2006-05-01 00:00:00
abstract::Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show tha...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1134
更新日期:2016-12-01 00:00:00