Bivalent hapten-bearing peptides designed for iodine-131 pretargeted radioimmunotherapy
| Autor: | Emilija Janevik-Ivanovska, M. Cohen, Emmanuel Gautherot, Anne Gruaz-Guyon, M. Hillairet de Boisferon, Gérard Milhaud, William Rostène, Jacques Barbet, A. Tartar |
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| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_treatment
Biomedical Engineering Pharmaceutical Science Mice Nude chemical and pharmacologic phenomena Bioengineering Peptide Bivalent (genetics) Iodine Radioisotopes chemistry.chemical_compound Mice Peptide synthesis medicine Tumor Cells Cultured Animals Humans Pretargeted Radioimmunotherapy Pretargeting Pharmacology chemistry.chemical_classification Mice Inbred BALB C integumentary system Chemistry Organic Chemistry Radioimmunotherapy Combinatorial chemistry In vitro Female Peptides Hapten Haptens Biotechnology |
| Zdroj: | Bioconjugate chemistry. 8(4) |
| ISSN: | 1043-1802 |
| Popis: | Pretargeting with bispecific antibodies has been used successfully for tumor detection and is now considered for radioimmunotherapy. The advantages of bivalent haptens have been demonstrated in this context. A series of bivalent molecules allowing efficient labeling with radioactive iodine has been designed for use with this new technology. They were based on the histamine-hemisuccinate hapten and prepared by solid phase peptide synthesis. Simultaneous binding of two antibody molecules to one bivalent hapten was possible with low steric hindrance when the two hapten groups were attached to the lateral chains of lysine residues separated by a single amino acid. Bispecific antibodies to the hapten and to carcinoembryonic antigen were shown to mediate specific binding of the haptens to tumor cells in vitro. These experiments demonstrated that the bivalent hapten AG3.0, with a lysyl-D-tyrosyl-lysine connecting chain, possessed the best binding properties. This peptide was used to target iodine-125 to human colon cancer xenografts in nude mice. High tumor uptake and tumor to normal tissue ratios were observed. This peptide thus appears as a good candidate for further development. Asymmetric bivalent haptens, with one histamine-hemisuccinate and one diethylenetriaminepentaacetic acid group, have also been prepared and shown to be capable of binding simultaneously two specific antibody molecules. These peptides should be useful to target radioiodine to cells characterized by the expression of two different antigenic markers. |
| Databáze: | OpenAIRE |
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