NDLI: Humanization of an anti-p185HER2 antibody for human cancer therapy.

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Light-induced phosphorylation of a membrane protein plays an early role in signal transduction for phototropism in Arabidopsis thaliana.

Extension growth of the water mold Achlya: interplay of turgor and wall strength.

Approximating Markov chains.

SNC1, a yeast homolog of the synaptic vesicle-associated membrane protein/synaptobrevin gene family: genetic interactions with the RAS and CAP genes.

Urate-null rosy mutants of Drosophila melanogaster are hypersensitive to oxygen stress.

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Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain.

In vitro replication of adeno-associated virus DNA.

Finding errors in DNA sequences.

Leucine-responsive regulatory protein controls the expression of both the pap and fan pili operons in Escherichia coli.

Humanization of an anti-p185HER2 antibody for human cancer therapy.

Development of antibodies against the rat brain somatostatin receptor.

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Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit.

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Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues.

Differential expression of c-fos and zif268 in rat striatum after haloperidol, clozapine, and amphetamine.

Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit.

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On the nature of global classification.

Theory of hydrophobicity: transient cavities in molecular liquids.

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Humanization of an anti-p185HER2 antibody for human cancer therapy.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Henner, D. Kotts, C. Carver, M. E. Shepard, H. M. Wong, W. L. Ridgway, J. B. Rowland, A. M. Carter, P. Presta, L. Gorman, C. M.
Description	Author Affiliation: Carter P ( Department of Protein Engineering, Genentech Inc., South San Francisco, CA 94080.);
Abstract	The murine monoclonal antibody mumAb4D5, directed against human epidermal growth factor receptor 2 (p185HER2), specifically inhibits proliferation of human tumor cells overexpressing p185HER2. However, the efficacy of mumAb4D5 in human cancer therapy is likely to be limited by a human anti-mouse antibody response and lack of effector functions. A 'humanized' antibody, humAb4D5-1, containing only the antigen binding loops from mumAb4D5 and human variable region framework residues plus IgG1 constant domains was constructed. Light- and heavy-chain variable regions were simultaneously humanized in one step by 'gene conversion mutagenesis' using 311-mer and 361-mer preassembled oligonucleotides, respectively. The humAb4D5-1 variant does not block the proliferation of human breast carcinoma SK-BR-3 cells, which overexpress p185HER2, despite tight antigen binding (Kd = 25 nM). One of seven additional humanized variants designed by molecular modeling (humAb4D5-8) binds the p185HER2 antigen 250-fold and 3-fold more tightly than humAb4D5-1 and mumAb4D5, respectively. In addition, humAb4D5-8 has potency comparable to the murine antibody in blocking SK-BR-3 cell proliferation. Furthermore, humAb4D5-8 is much more efficient in supporting antibody-dependent cellular cytotoxicity against SK-BR-3 cells than mumAb4D5, but it does not efficiently kill WI-38 cells, which express p185HER2 at lower levels.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Monoclonal Genetics Immunotherapy Protein-Tyrosine Kinases Immunology Proto-Oncogene Proteins Proto-Oncogenes Receptor, Epidermal Growth Factor Adenocarcinoma Amino Acid Sequence Therapeutic Use Breast Neoplasms Cell Division Cell Line, Transformed Chimera Cloning, Molecular Enzyme-Linked Immunosorbent Assay Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulin Variable Region Models, Molecular Molecular Sequence Data Oligodeoxyribonucleotides Oligonucleotides, Antisense Polymerase Chain Reaction Protein Conformation Receptor, ErbB-2 Restriction Mapping Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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