Abstract:
:Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. We engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors. To this end, the constant region of the human gamma 1 chain was mutated by deleting the second domain (CH2). Here we show that the CH2-deleted antibody (ch14.18-delta CH2) was cleared from the blood of athymic (nu/nu) mice bearing human melanoma tumors with the same kinetics as human IgG F(ab')2. At a beta t1/2 of 12 hr, 0.9% of the injected dose of 125I-labeled ch14.18-delta CH2 was found per milliliter of blood 24 hr after i.v. injection. In biodistribution experiments, 125I-labeled ch14.18-delta CH2 targeted specifically to melanoma xenografts, achieving optimal tumor-to-tissue ratios 12-16 hr after i.v. injection. ch14.18-delta CH2 was localized to the melanoma tumors more rapidly and with better localization ratios than the intact chimeric antibody ch14.18. Sixteen hours after i.v. injection, the tumor-to-blood and tumor-to-liver ratios of ch14.18-delta CH2 were 5 and 12, respectively, while optimal localization ratios obtained for ch14.18 were 1 and 5, respectively, but 96 hr after injection. A reagent such as ch14.18-delta CH2 should be useful for radioimmunodetection of human tumors because of reduced immunogenicity, increased targeting specificity, and rapid clearance from circulation.
journal_name
Proc Natl Acad Sci U S Aauthors
Mueller BM,Reisfeld RA,Gillies SDdoi
10.1073/pnas.87.15.5702subject
Has Abstractpub_date
1990-08-01 00:00:00pages
5702-5issue
15eissn
0027-8424issn
1091-6490journal_volume
87pub_type
杂志文章abstract::Most organisms are evolutionary conservatives; they may subdivide their niches but tend to remain within them. Yet the fossil record shows many cases of breakthrough to a new mode of life. How may such evolutionary innovation be recognized at this time level? Three species of Drosophila have accomplished an innovation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.9.3517
更新日期:1974-09-01 00:00:00
abstract::The major auxin-binding protein in maize membranes is thought to function as a physiological receptor. From earlier information, including the use of site-directed irreversible inhibitors, several of the amino acids likely to form part of the active auxin-binding site were provisionally assigned. Inspection of the ami...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.7208
更新日期:1992-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.2.604
更新日期:1999-01-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.90.20.9320
更新日期:1993-10-15 00:00:00
abstract::Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.10.3685
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abstract::Inhibitory postsynaptic currents occurring spontaneously in the teleost Mauthner cell were analyzed with the single-electrode voltage-clamp technique. They were collected during depolarizing steps and were outward-going; this procedure allowed them to be isolated from possible excitatory currents flowing in the opposi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.16.5981
更新日期:1987-08-01 00:00:00
abstract::The concepts of source and quantum action principle are used to produce the phonon Green's function appropriate for an initial phonon vacuum state. An application to the Mossbauer effect is presented. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.15.6537
更新日期:1991-08-01 00:00:00
abstract::Intracellular transport is interspersed with frequent reversals in direction due to the presence of opposing kinesin and dynein motors on organelles that are carried as cargo. The cause and the mechanism of reversals are unknown, but are a key to understanding how cargos are delivered in a regulated manner to specific...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.13.4700
更新日期:1988-07-01 00:00:00
abstract::The mechanisms that regulate insulin secretion were investigated using capacitance measurements of exocytosis in single beta cells maintained in tissue culture. Exocytosis was stimulated by voltage-clamp depolarizations to activate the voltage-dependent Ca2+ channels that mediate Ca2+ influx into the beta cell. Under ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.10.4343
更新日期:1994-05-10 00:00:00
abstract::An important goal in biology is to predict from sequence data the high-resolution structures of proteins and the interactions that occur between them. In this paper, we describe a computational approach that can make these types of predictions for a series of coiled-coil dimers. Our method comprises a dual strategy th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.261563398
更新日期:2001-12-18 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2019-06-25 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1217611110
更新日期:2013-03-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0810794106
更新日期:2009-01-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611613104
更新日期:2007-09-11 00:00:00
abstract::We have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken beta-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in pri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.16.5976
更新日期:1988-08-01 00:00:00
abstract::The putative oxidation of hydroethidine (HE) has become a widely used fluorescent assay for the detection of superoxide in cultured cells. By covalently joining HE to a hexyl triphenylphosphonium cation (Mito-HE), the HE moiety can be targeted to mitochondria. However, the specificity of HE and Mito-HE for superoxide ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601945103
更新日期:2006-10-10 00:00:00
abstract::Climate change and resource exploitation have been shown to modify the importance of bottom-up and top-down forces in ecosystems. However, the resulting pattern of trophic control in complex food webs is an emergent property of the system and thus unintuitive. We develop a statistical nondeterministic model, capable o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.9.4107
更新日期:1978-09-01 00:00:00
abstract::Animals and plants use modified cell cycles to achieve particular developmental strategies. In one common example, most animals and plants have tissues in which the cells become polyploid or polytene by means of an S-G cycle, but the mechanism by which mitosis is inhibited in the endo cycle is not understood. The Dros...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2002-08-20 00:00:00
abstract::The total synthesis of the sialic acid-containing antigenic epitope fucose GM(1) (Fuc-GM(1)) by an improved reactivity-based one-pot synthetic strategy is reported. Based on a thioglycoside reactivity database, three saccharide building blocks, 3, 4, and 5, were designed and prepared to incorporate a descending order ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0337590100
更新日期:2003-02-04 00:00:00
abstract::Plasma levels of corticosterone are often used as a measure of "stress" in wild animal populations. However, we lack conclusive evidence that different stress levels reflect different survival probabilities between populations. Galápagos marine iguanas offer an ideal test case because island populations are affected d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.131091498
更新日期:2001-06-19 00:00:00
abstract::Decisions always involve both facts and values, whereas most science communication focuses only on facts. If science communication is intended to inform decisions, it must be competent with regard to both facts and values. Public participation inevitably involves both facts and values. Research on public participation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1212740110
更新日期:2013-08-20 00:00:00
abstract::A highly purified fraction obtained from scrapie (263-K strain)-infected hamsters' brains by an alternative procedure without proteinase K treatment contained a protease-resistant form of the scrapie precursor protein (PrPSc) and infectivity of 9.9 +/- 0.7 log LD50/ml. Polyclonal antibodies produced against hamster sc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.16.6373
更新日期:1990-08-01 00:00:00
abstract::The canonical function of the human telomerase protein (hTERT) is to synthesize telomeric DNA, but it has other biological activities, including enhancing cell proliferation, decreasing apoptosis, regulating DNA damage responses, and increasing cellular proliferative lifespan. The mechanistic relationships among these...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-12-13 00:00:00
abstract::Peripheral blood mononuclear cells of 10 out of 26 patients with human immunodeficiency virus type 1 (HIV-1) released IgE-binding factors, as determined by two independent assays. The formation of the factors by the mononuclear cells was enhanced by incubation of the cells with homologous IgE. In the presence of IgE, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.23.9214
更新日期:1988-12-01 00:00:00
abstract::Antibody-coated latex beads (Ab-beads) were attached to Leptospira interrogans serovars illini 3055 and icterohaemorrhagiae SC1157. The movement of the Ab-beads relative to the motion of the cells was observed by direct darkfield microscopy or was recorded on videotape. When the Ab-beads were attached to the front end...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.11.7166
更新日期:1981-11-01 00:00:00
abstract::A 32-base-pair (bp) DNA duplex with deletions in one strand, and thus extra bases in the opposing strand, was ligated head-to-tail to produce linear and circular multimers. The electrophoretic mobility of the linear multimers was analyzed in polyacrylamide gels and the size of the circular DNA was determined by electr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.13.4833
更新日期:1989-07-01 00:00:00