Lowering the isoelectric point of the Fv portion of recombinant immunotoxins leads to decreased nonspecific animal toxicity without affecting antitumor activity

Cancer Research

Volumn 61, Issue 13, 2001, Pages 5070-5077

  Onda, Masanori ^a   Nagata, Satoshi ^a   Tsutsumi, Yasuo ^a   Vincent, James J ^a   Wang, Qing cheng ^a   Kreitman, Robert J ^a   Lee, Byungkook ^a   Pastan, Ira ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CD22 ANTIGEN; IMMUNOTOXIN; INTERLEUKIN 2 RECEPTOR; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; COLON CANCER; CYTOTOXICITY; DOSE RESPONSE; GENETIC ENGINEERING; HUMAN; HUMAN CELL; ISOELECTRIC POINT; MOUSE; MUTAGENESIS; MUTATION; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL;

ADP RIBOSE TRANSFERASES; ALANINE TRANSAMINASE; AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES; BACTERIAL TOXINS; DISULFIDES; EXOTOXINS; FEMALE; IMMUNOGLOBULIN FRAGMENTS; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOTOXINS; ISOELECTRIC POINT; LIVER; MICE; MOLECULAR SEQUENCE DATA; MUTAGENESIS; NEOPLASMS, EXPERIMENTAL; RECOMBINANT PROTEINS; VIRULENCE FACTORS;

EID: 0035394359     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (30)

1. Recombinant toxins for cancer treatment
2. A recombinant immunotoxin consisting of 2 antibody variable domains fused to Pseudomonas exotoxin
3. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms
4. Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichea coli
5. A comparison of strategies to stabilize immunoglobulin Fv-fragments
6. A recombinant immunotoxin containing a disulfide-stabilized Fv
7. Stabilization of the Fv fragments in recombinant immunotoxins by disulfide bonds engineered into conserved framework regions
8. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in Escherichia coli
9. Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas
10. Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with anti-tumor activity
11. Improving antibody affinity by mimicking somatic hypermutation in vitro
12. Responses in refractory hairy celt leukemia to a recombinant immunotoxin
13. Phase I trial of recombinant immunotoxin anti-Tac(Fv)PE38 (LMB-2) in patients with hematologic malignancies
14. Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RPB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias
15. Inhibition of TNF-α produced by Kupffer cells protects against the non-specific liver toxicity of immunotoxin anti-Tac(Fv)-PE38, LMB-2
16. Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point
17. Rapid and efficient site-specific mutagenesis without phenotypic selection
18. B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice
19. Trimmed Spearman-Karber method for estimating median lethal concentration in toxicity bioassays
20. The median lethal dose and its estimation
21. Improved stability and yield of a Fv-toxin fusion protein by computer design and protein engineering of the Fv
22. Engineering antibody Fv fragments for cancer detection and therapy: Disulfide-stabilized Fv fragments
23. Augmentation and suppression of release of tumor necrosis factor from macrophages by negatively charged phospholipids
24. Accumulation of a recombinant immunotoxin in a tumor in vivo: Fewer than 1000 molecules per cell are sufficient for complete responses
25. Glomerular permselectivity: Barrier function based on discrimination of molecular size and charge
26. Effect of isoelectric point on biodistribution and inflammation - Imaging with indium-111-labeled IgG
27. Charge-modified single chain antibody constructs of monoclonal antibody CC49: Generation, characterization, pharmacokinetics, and biodistribution analysis
28. The pharmacokinetic characteristics of glycolated humanized anti-Tac Fabs are determined by their isoelectric points
29. Chemical modification to reduce renal uptake of disulfide-bonded variable region fragment of anti-Tac monoclonal antibody labeled with Tc-99m
30. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons