Category Archives: Proc Natl Acad Sci U S A

Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange.

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Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange.

Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5145-50

Authors: Labrijn AF, Meesters JI, de Goeij BE, van den Bremer ET, Neijssen J, van Kampen MD, Strumane K, Verploegen S, Kundu A, Gramer MJ, van Berkel PH, van de Winkel JG, Schuurman J, Parren PW

Abstract
The promise of bispecific antibodies (bsAbs) to yield more effective therapeutics is well recognized; however, the generation of bsAbs in a practical and cost-effective manner has been a formidable challenge. Here we present a technology for the efficient generation of bsAbs with normal IgG structures that is amenable to both antibody drug discovery and development. The process involves separate expression of two parental antibodies, each containing single matched point mutations in the CH3 domains. The parental antibodies are mixed and subjected to controlled reducing conditions in vitro that separate the antibodies into HL half-molecules and allow reassembly and reoxidation to form highly pure bsAbs. The technology is compatible with standard large-scale antibody manufacturing and ensures bsAbs with Fc-mediated effector functions and in vivo stability typical of IgG1 antibodies. Proof-of-concept studies with HER2×CD3 (T-cell recruitment) and HER2×HER2 (dual epitope targeting) bsAbs demonstrate superior in vivo activity compared with parental antibody pairs.

PMID: 23479652 [PubMed – indexed for MEDLINE]

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Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells.

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Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells.

Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2928-33

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Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric G proteins and is important for development and chemotaxis.

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Dictyostelium Ric8 is a nonreceptor guanine exchange factor for heterotrimeric G proteins and is important for development and chemotaxis.

Proc Natl Acad Sci U S A….

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Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans.

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Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans.

Proc Natl Acad Sci U S A. 2012 Dec…

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How DNA-repair proteins find their targets.

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How DNA-repair proteins find their targets.

Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18243-4

Authors: Quessada-Vial A, van Oijen AM

PMID:…

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Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation.

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Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation.

Proc Natl Acad Sci U S A. 2012 Oct…

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Structural divergence of paralogous S components from ECF-type ABC transporters.

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Structural divergence of paralogous S components from ECF-type ABC transporters.

Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):13990-5

Authors: Berntsson…

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Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation.

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Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation.

Proc Natl Acad Sci U S A. 2012 Sep…

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Hydrophobic gating of mechanosensitive channel of large conductance evidenced by single-subunit resolution.

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Hydrophobic gating of mechanosensitive channel of large conductance evidenced by single-subunit resolution.
Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12944-9
Authors: Birkner JP, Poolman B, Koçer A
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Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.

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Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.
Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10322-7
Authors: Gilsbach BK, Ho FY, V… Continue reading

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Primary somatosensory cortex discriminates affective significance in social touch.

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Primary somatosensory cortex discriminates affective significance in social touch.

Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):E1657-66

Authors: Gazzola…

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Pupil dilation deconvolution reveals the dynamics of attention at high temporal resolution.

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Pupil dilation deconvolution reveals the dynamics of attention at high temporal resolution.
Proc Natl Acad Sci U S A. 2012 May 29;109(22):8456-60
Authors: Wierda SM, van Rijn H, Taatgen NA, Martens S
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Global changes in diets and the consequences for land requirements for food.

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Global changes in diets and the consequences for land requirements for food.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):6868-72
Authors: Kastner T, Rivas MJ, Koch W, Nonhebel S
Abstract
Provi… Continue reading

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Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP.

Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP.
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E905-13
Authors: Beilharz K, Nováková L, Fadda D, Branny P, Massidda O, Veenin… Continue reading

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Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory.

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory.

Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3504-9

Authors: …

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Cross-cultural experiments are more useful when explanans and explanandum are separated.

Cross-cultural experiments are more useful when explanans and explanandum are separated.

Proc Natl Acad Sci U S A. 2012 Apr 17;

Authors: van Hoorn A

PMID: 22511721 [PubMed…

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Microbial diversity determines the invasion of soil by a bacterial pathogen.

Microbial diversity determines the invasion of soil by a bacterial pathogen.

Proc Natl Acad Sci U S A. 2012 Jan 9;

Authors: van Elsas JD, Chiurazzi M, Mallon CA, Elhottova D,…

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Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity.

Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity.

Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15925-30

Authors: Fawcett TW,…

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Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography.

Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography.

Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15196-200

Authors: …

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HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺ T lymphocytes.

HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺ T lymphocytes.

Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10656-61

Authors: Gooden M, Lampen M,…

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