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РЖ ВИНИТИ 76 (BI29) 96.06-04Н1.406

Rapid humanization of the Fv of monoclonal antibody B3 by using framework exchange of the recombinant immunotoxin B3(Fv)-PE38 [Text] / Inai Benhar [et al.] // Proc. Nat. Acad. Sci. USA. - 1994. - Vol. 91, N 25. - P12051-12055 . - ISSN 0027-8424
Перевод заглавия: Быстрая гуманизация [региона] F[v] моноклонального антитела B3 при использовании структурных замен в рекомбинантном иммунотоксине B3 (Fv)-PE38
Аннотация: B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of carcinoma-specific antibody B3 is fused to a fruncated form of Pseudomonas exotoxin (PE). Here we describe the humanization of the Fv of B3(Fv)-PE38 by "framework exchange." The variable domains of the heavy (V[H]) and light (V[L]) chains were aligned with their best human homologs to identify framework residues that differ. Initially, 11 framework residues in V[H] and six in V[L] were changed by site-specific mutagenesis to human residues. This basic design resulted in some 20-fold loss of activity. Changing V[L] residues at the interdomain interfacial position 100 and at the buried position 104 to the human sequence increased the activity 8-fold. Changing V[H] residue at position 82b from the human sequence back to that of the mouse restored the activity 2- to 3-fold to the full binding and cytotoxic activity of the mouse sequence. Humanized B3(Fv)-PE38 lost immunogenic epitopes recognized by sera from monkeys that had been immunized with B3(Fv)-PE38. США, Lab. Mol. Biol., Div. Cancer Biol., Diagnosis and Centers, Nat. Cancer Inst., Building 37, Room 4E16; Nat. Inst. of Health, 900 Rockville Pike, Bethesda, MD 20892. Библ. 36

ГРНТИ	76.29.49

ВИНИТИ 761.29.49.23.05
Рубрики: РЕКОМБИНАНТНЫЕ БЕЛКИ
ИММУНОТОКСИНЫ
FV-РАЙОН АНТИТЕЛ B3
ЭКЗОТОКСИН PSEUDOMONAS
ГУМАНИЗАЦИЯ FV

Доп.точки доступа:
Benhar, Inai; Padlan, Eduardo A.; Jung, Sun-Hee; Lee, Byungkok; Pastan, Ira

РЖ ВИНИТИ 34 (BI39) 96.06-04К1.98

Rapid humanization of the Fv of monoclonal antibody B3 by using framework exchange of the recombinant immunotoxin B3(Fv)-PE38 [Text] / Inai Benhar [et al.] // Proc. Nat. Acad. Sci. USA. - 1994. - Vol. 91, N 25. - P12051-12055 . - ISSN 0027-8424
Перевод заглавия: Быстрая гуманизация [региона] F[v] моноклонального антитела B3 при использовании структурных замен в рекомбинантном иммунотоксине B3 (Fv)-PE38
Аннотация: B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of carcinoma-specific antibody B3 is fused to a fruncated form of Pseudomonas exotoxin (PE). Here we describe the humanization of the Fv of B3(Fv)-PE38 by "framework exchange." The variable domains of the heavy (V[H]) and light (V[L]) chains were aligned with their best human homologs to identify framework residues that differ. Initially, 11 framework residues in V[H] and six in V[L] were changed by site-specific mutagenesis to human residues. This basic design resulted in some 20-fold loss of activity. Changing V[L] residues at the interdomain interfacial position 100 and at the buried position 104 to the human sequence increased the activity 8-fold. Changing V[H] residue at position 82b from the human sequence back to that of the mouse restored the activity 2- to 3-fold to the full binding and cytotoxic activity of the mouse sequence. Humanized B3(Fv)-PE38 lost immunogenic epitopes recognized by sera from monkeys that had been immunized with B3(Fv)-PE38. США, Lab. Mol. Biol., Div. Cancer Biol., Diagnosis and Centers, Nat. Cancer Inst., Building 37, Room 4E16; Nat. Inst. of Health, 900 Rockville Pike, Bethesda, MD 20892. Библ. 36

ГРНТИ	34.43.33

ВИНИТИ 341.43.33.05
Рубрики: РЕКОМБИНАНТНЫЕ БЕЛКИ
ИММУНОТОКСИНЫ
FV-РАЙОН АНТИТЕЛ B3
ЭКЗОТОКСИН PSEUDOMONAS
ГУМАНИЗАЦИЯ FV

Доп.точки доступа:
Benhar, Inai; Padlan, Eduardo A.; Jung, Sun-Hee; Lee, Byungkok; Pastan, Ira

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