ライフサイエンスコーパス: diabody

1 dose (0.1, 1.0, or 10 Eq with respect to the diabody).

2 y fragments, creating bispecific antibodies (diabodies).

3 he C6ML3-9 diabody to 15-fold for the C6G98A diabody.

4 for an anti-tumor-associated glycoprotein 72 diabody.

5 trast images at 18 h for the (124)I-anti-CEA diabody.

6 ding presumably also selects for more stable diabodies.

7 Early administration of diabody (0.8 mg/kg) caused a twofold decrease in brain l

8 Prophylactic administration of the diabody (0.8 mg/kg) in a thromboplastin-induced model of

9 odistribution of the 18F-fluorobenzyl-T84.66 diabody (18F-FB-T84.66 diabody) was evaluated in athymic

10 Similar values were obtained for the (124)I-diabody (3.95 at 4 h and 10.93 at 18 h).

11 (89)Zr-desferrioxamine-labeled anti-CD8 cys-diabody ((89)Zr-malDFO-169 cDb) for noninvasive immuno-P

12 d anti-carcinoembryonic antigen (CEA) T84.66 diabody, a genetically engineered noncovalent dimer of s

13 model of cerebral ischemia and reperfusion, diabody administration (0.8 mg/kg, 1 hour postocclusion)

14 Diabodies also elicited biased or differential activatio

15 The Di-diabody also inherited the biological properties from bo

16 ibody or with 3.1 MBq (85 microCi) of (124)I-diabody and imaged at 4 and 18 h by PET.

17 he structure of a complex between a bivalent diabody and its antigen, influenza neuraminidase, has be

18 uptake levels than did the smaller formats (diabody and scFv).

19 r N-terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP) formats that yield

20 kidney uptake and retention of non-PEGylated diabody and that the two have similarly high tumor uptak

21 h cells, the molecule was expressed in scFv, diabody and triabody formats in a number of cell lines t

22 ere n indicates the number of TCO groups per diabody) and radiolabeled tetrazine to optimize the TCO

23 ication grade (0, 1.8, or 4.7 TCO groups per diabody) and the (177)Lu-tetrazine dose (0.1, 1.0, or 10

24 as 1 h after injection of the 18F-FB-T84.66 diabody, and only a background level of activity accumul

25 Db9C2 diabody (anti-group I) and the Db4C1op diabody (anti-AahII), the latter being modified to facil

26 The mixture consists of the Db9C2 diabody (anti-group I) and the Db4C1op diabody (anti-Aah

27 Diabodies are capable of substantial accumulation in tum

28 Diabodies are noncovalent dimers of single-chain antibod

29 Such diabodies are produced in a cell-free protein expression

30 With a Mr of approximately 55,000, diabodies are rapidly cleared from the circulation, resu

31 ooctene (TCO)-functionalized TAG72 targeting diabody, AVP04-07, and a low-molecular-weight radiolabel

32 Diabody binding kinetics were determined by surface plas

33 The Di-diabody binds to both EGFR and IGFR and effectively bloc

34 athymic mice with both the chemical and the diabody bispecific proteins.

35 ssociate and reassociate to form a dimer, or diabody, but in which symmetric back-to-back contacts be

36 in the kidney, the use of radiometal-labeled diabodies can be problematic for both imaging and therap

37 The 18F-FB-T84.66 diabody can be used for high-contrast small-animal PET i

38 in vivo, we generated anti-CD4 and -CD8 cys-diabodies (cDbs) derived from the parental antibody hybr

39 The PEG27 and PEG12 diabody conjugates also demonstrated low kidney uptake w

40 beled with (64)Cu, the DOTA-PEG12 and -PEG27 diabody conjugates gave high-contrast PET images of colo

41 9 F(ab')(2) and a fully humanized bispecific diabody construct (BS1.5H), expressed in Escherichia col

42 In fact, the diabody constructed from the lowest affinity scFv exhibi

43 These noncognate B cells, decorated with the diabody, could then stimulate the more rare Id-specific

44 nsistent with the maximum possible number of diabody cross-links.

45 We utilized diabodies (DA) as surrogate ligands in a prototypical di

46 ti-prostate-specific membrane antigen (PSMA) diabody (Db) and minibody (Mb), were compared with intac

47 tion of an Id vaccine, we engineered a small diabody (Db) molecule containing both a B-cell-targeting

48 nhibitor against TAFI and PAI-1 (heterodimer diabody, Db-TCK26D6x33H1F7) in several mouse models of t

49 isingly, the differences in affinity between diabodies did not result in differences in quantitative

50 In contrast to tPA, the diabody did not increase accumulative bleeding.

51 When using the BS1.5H diabody for pretargeting, tumor-to-blood, tumor-to-liver

52 for the HER2 receptor tyrosine kinase (C6.5 diabody) for its ability to function as a PET radiotrace

53 uman CD3 mAb v9 in a clinically investigated diabody format known as Dual-Affinity Re-Targeting (DART

54 This diabody format, when combined with the power of phage di

55 ycol (PEG)3400-anti-carcinoembryonic antigen diabody has less than half the kidney uptake and retenti

56 reviously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction

57 Diabody-induced signaling amplitudes varied from full to

58 Non-signaling diabodies inhibited proliferation of erythroid precursor

59 labeled tetrazine was injected at 47 h after diabody injection, and mice were euthanized 3 h later.

60 We also show that the presence of both diabodies is necessary for the animals to survive.

61 Furthermore, the diabody is a stronger inhibitor than its parent antibodi

62 The present work evaluated the minibody or diabody labeled with (124)I, for imaging tumor-bearing m

63 Phage diabody libraries enable screening or selection of the b

64 Peptide epitopes present in the diabody linker augmented the response by activating CD4(

65 PEGylated diabodies may be a valuable platform for delivery of rad

66 These diabodies may have therapeutic applications requiring th

67 Diabodies may provide a useful approach to the structure

68 Such bispecific diabodies may provide an attractive alternative to monoc

69 Thus, diabodies may represent an effective molecular structure

70 dual receptor blockade with the bifunctional diabody may prove to be a more efficient approach in inh

71 Engineered antibody fragments, such as diabodies, minibodies, and single-chain Fv (scFv) -Fc, h

72 Here, we report the use of a diabody mixture in which the molar ratio matches the cha

73 e intraperitoneal injection of 30 mug of the diabody mixture protected almost all the mice exposed to

74 18F labeling of the anti-CEA T84.66 diabody (molecular mass, 55 kDa) was achieved with N-suc

75 association rate constants obtained for each diabody molecule were similar to that of the parental (c

76 Antitumor diabody molecules are noncovalent single-chain Fv dimers

77 dicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for

78 Here, we have constructed bivalent diabody molecules from three affinity mutants of the hum

79 detailed to create repertoires of bispecific diabody molecules with variability on one or both of the

80 gment [scFv]-C(H)3 dimer, 80 kDa) and T84.66 diabody (noncovalent dimer of scFv, 55 kDa) exhibit phar

81 was increased fivefold compared to a control diabody of the same molecular weight.

82 Delayed administration of diabody or tPA had no effect on lesion size, whereas the

83 om 33% to 88%, and immunoreactivity was 42% (diabody) or >90% (minibody).

84 Tumor accumulation of the diabody peaked at 3 h, reaching a much lower level (3.7

85 s currently conducting time-dependent (124)I diabody PET and necropsy comparative studies with larger

86 applied to in vivo (124)I anti-HER2/neu C6.5 diabody PET data and compared with necropsy biodistribut

87 The (124)I diabody PET image of a mouse with a tumor xenograft was

88 The addition of PEG3400 to the diabody reduced kidney uptake to a level (approximately

89 The 18F-labeled diabody represents a new class of tumor-specific probes

90 ingle-chain Fv and a bispecific single-chain diabody, respectively.

91 300 microCi (300 microg) 90Y-CHX-A"-C6.5K-A diabody resulted in only a minor delay in the growth of

92 The diabody retained the capacity to bind both KDR and Flt-1

93 We therefore engineered a bispecific scFv diabody (scDb) combining affinities for both c-erbB2 and

94 The 18F-FB-T84.66 diabody showed rapid and high tumor uptake and fast clea

95 PET images using (124)I-labeled minibody or diabody showed specific localization to the CEA-positive

96 Eq of (177)Lu-tetrazine with respect to the diabody showed the most promising biodistribution.

97 The IgG, diabody, single-chain variable domain (scFv), and novel

98 The scFv used to create the diabodies span a 133-fold range of affinity for the same

99 an chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Pla

100 Finally, the Di-diabody strongly inhibited the growth of two different h

101 tegy based on a covalently linked bispecific diabody structure that we term dual-affinity re-targetin

102 ers that is consistent with a domain-swapped diabody structure.

103 ion is discussed in terms of a new model for diabody structures, in which the V(H) and V(L) domains i

104 150 microCi (200 microg) 90Y-CHX-A"-C6.5K-A diabody substantially inhibits the growth rates of estab

105 re we constructed a recombinant bifunctional diabody that is capable of blocking both Flt-1 and KDR f

106 0 (t1/2, 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tum

107 ing from only 3-fold for that of the C6ML3-9 diabody to 15-fold for the C6G98A diabody.

108 e the use of a bispecific antibody fragment (diabody) to recruit the whole spectrum of antibody effec

109 gments (Fab, scFv)) and engineered variants (diabodies, triabodies, minibodies and single-domain anti

110 ical cross-linking methods and as bispecific diabodies using recombinant DNA technologies.

111 ant human IgG-like bispecific antibody, a Di-diabody, using the variable regions from two antagonisti

112 One diabody was able to recruit C1q, resulting in efficient

113 rebral artery occlusion, the efficacy of the diabody was compared to the standard thrombolytic treatm

114 One arm of the diabody was directed against the target antigen, and the

115 The diabody was expressed in Escherichia coli and purified b

116 At 24 h, 3-37-fold more diabody was retained in tumor compared with the parental

117 g from 18F-SFB, and the tracer 18F-FB-T84.66 diabody was synthesized with a specific activity of 1.83

118 F-fluorobenzyl-T84.66 diabody (18F-FB-T84.66 diabody) was evaluated in athymic nude mice bearing subc

119 The bispecific diabodies were able to recruit complement, induce mononu

120 AVP04-07 diabodies were functionalized with TCO tags, and in vitr

121 ion rate constants obtained for the bivalent diabodies were up to 15-fold slower.

122 re rapidly cleared from circulation, and the diabody, which accumulated in the tumor, may be more sui

123 neuraminidase tetramers cross-linked by four diabodies with 422 point symmetry.

124 size, whereas the combined administration of diabody with tPA caused a 1.7-fold decrease in lesion si