ライフサイエンスコーパス: costimulation blockade

1 sphamide in combination with CTLA4Ig-based T-costimulation blockade.

2 n of individuals most likely to benefit from costimulation blockade.

3 llograft survival in recipients treated with costimulation blockade.

4 ipheral transplantation tolerance induced by costimulation blockade.

5 tion of transplantation tolerance induced by costimulation blockade.

6 ss resist prolongation of skin allografts by costimulation blockade.

7 allograft survival was readily prolonged by costimulation blockade.

8 of sublethally irradiated mice treated with costimulation blockade.

9 es some of the survival advantage induced by costimulation blockade.

10 T cell apoptotic pathway, on the effects of costimulation blockade.

11 l for the induction of hyporesponsiveness by costimulation blockade.

12 opoietic chimerism, lymphocyte depletion and costimulation blockade.

13 lloantibody formation is susceptible to CD28 costimulation blockade.

14 olve depletion of immune effector cells with costimulation blockade.

15 gy induction and improves the efficacy of B7 costimulation blockade.

16 ral helper T cells, were highly sensitive to costimulation blockade.

17 lanted tissues when induced by coreceptor or costimulation blockade.

18 r saturation as a pharmacodynamic measure of costimulation blockade.

19 partial regimens, or a full regimen based on costimulation blockade.

20 tic and skin allografts in mice treated with costimulation blockade.

21 dramatically prolonged graft survival under costimulation blockade.

22 slet allograft survival in mice treated with costimulation blockade.

23 deficient mice show early graft loss despite costimulation blockade.

24 for long-term allograft survival induced by costimulation blockade.

25 skin allograft survival in mice treated with costimulation blockade.

26 ection driven by CD8(+) T cells resistant to costimulation blockade.

27 graft survival was compared in untreated and costimulation blockade (500 microg anti-CD40L and 500 mi

28 - mice than in IFN-gamma+/+ mice, and T-cell costimulation blockade abrogated alloantigen-induced T-c

29 We demonstrated that costimulation blockade after allogeneic heart transplant

30 red a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals

31 In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and ef

32 eplacement of a calcineurin inhibitor with a costimulation blockade agent, but this does not appear t

33 by treating mice with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimula

34 -/-) mice treated with either B7-CD28 T-cell costimulation blockade alone or B7-CD28 T-cell costimula

35 we find that the full tolerance regimen, or costimulation blockade alone, specifically inhibits alre

36 graft survival beyond that in mice receiving costimulation blockade alone.

37 Late costimulation blockade also reduced virus-specific T-cel

38 after a 2- to 4-month delay, plus short-term costimulation blockade and calcineurin inhibitor treatme

39 neutralizing IL-4 in addition to CD40-CD154 costimulation blockade and CD8+ T-cell depletion prevent

40 ng protocol with ABT-737 in combination with costimulation blockade and low-dose cyclosporine A resul

41 that makes use of the synergistic effects of costimulation blockade and mTOR inhibition.

42 pregnancy alone, we examined the efficacy of costimulation blockade and proteasome inhibition for des

43 cy may be a valid pharmacodynamic measure of costimulation blockade and provide the first direct clin

44 Combined use of costimulation blockade and rapamycin may provide a means

45 Costimulation Blockade and Sirolimus (CoBS) resulted in

46 etermined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this diseas

47 ce immunosuppression with CD28/CD40-directed costimulation blockade and sirolimus.

48 gate the role of innate immunity, mice given costimulation blockade and skin allografts were coinject

49 te induction of transplantation tolerance by costimulation blockade and that IL-2/Idd3 is a critical

50 stem cell transplantation protocols based on costimulation blockade and tolerance induction may requi

51 We took cell/complement depletion, costimulation blockade, and serum transfer approaches to

52 ed strategy using a single dose of busulfan, costimulation blockade, and T cell-depleted donor bone m

53 C57BL/6 mice treated with costimulation blockade are able to generate allospecific

54 s, rather than exerting immune modulation by costimulation blockade as currently postulated.

55 t a donor-specific CD8 T cell response under costimulation blockade as well as for the graft to survi

56 ss a full MHC disparity using peritransplant costimulation blockade-based approaches, but unexpectedl

57 ansion and combinatorial therapy with novel, costimulation blockade-based immunosuppression strategie

58 ed-efficacy as in young recipients employing costimulation blockade-based or T-cell depletion-based c

59 urmount these impediments, we have adapted a costimulation blockade-based protocol developed for soli

60 Costimulation blockade-based regimens are a promising st

61 , belatacept, rapamycin protocol, or similar costimulation blockade-based regimens, in pursuit of non

62 gents currently available, in particular, by costimulation blockade-based regimens.

63 roduction may represent an important part of costimulation blockade-based strategies to promote allog

64 However, costimulation blockade-based tolerance protocols have fa

65 an attractive substitute in mouse models of costimulation blockade-based tolerance regimens.

66 me inhibitor (PI) based desensitization with costimulation blockade (belatacept) to mitigate germinal

67 investigational arm using low-dose CNI plus costimulation blockade (belatacept) with intended CNI wi

68 In contrast, following treatment with costimulation blockade, busulfan, and bone marrow, heart

69 bed a nonirradiation-based regimen combining costimulation blockade, busulfan, and donor bone marrow

70 in chemically diabetic NOD mice treated with costimulation blockade but is prolonged further in NOD I

71 rapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies w

72 We previously reported that costimulation blockade by abatacept limits the decline o

73 previously reported that continuous 24-month costimulation blockade by abatacept significantly slows

74 that TLR signaling abrogates the effects of costimulation blockade by preventing alloreactive CD8+ T

75 These results demonstrate that costimulation blockade can induce hyporesponsiveness of

76 Rapamycin together with costimulation blockade can induce tolerance in organ all

77 It has been reported that costimulation blockade can result in T cell anergy.

78 d depletion of CD4 and/or CD8 pos T cells or costimulation blockade can substitute for ALS and preser

79 ells (Tmem), particularly those resistant to costimulation blockade (CB), are a major barrier to tran

80 c process dependent on the level of residual costimulation blockade, CD4+ regulatory cells, and activ

81 In synchimeric mice treated with costimulation blockade, coadministration of all four TLR

82 ich donor-specific tolerance is induced with costimulation blockade (CoB) plus donor-specific transfu

83 Belatacept, a B7-specific mediator of costimulation blockade (CoB), is clinically indicated as

84 Costimulation blockade (CoB)-based immunosuppression off

85 s trial was conducted to determine whether a costimulation blockade (CoB)-based regimen could achieve

86 during the response to both inflammation and costimulation blockade (CoB).

87 stimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte tr

88 stimulation blockade alone or B7-CD28 T-cell costimulation blockade combined with donor splenocyte tr

89 th on IFN-gamma-deficient recipients despite costimulation blockade could be explained by the lack of

90 We tested whether peri-transplant costimulation blockade could prolong VCA survival and re

91 ng Tregs with donor cells in the presence of costimulation blockade (CSB-Tregs); and (3) transducing

92 ly tolerized by either rapamycin or combined costimulation blockade (CTLA-4Ig plus anti-CD40L mAb).

93 Mice receiving costimulation blockade (CTLA4-Ig and anti-CD40 ligand) a

94 tive preconditioning (low-dose busulfan) and costimulation blockade (CTLA4-Ig and anti-CD40L) to prod

95 NOD.B6 Idd3 mice treated with costimulation blockade deleted alloreactive CD8 T-cells

96 In a mouse model of costimulation blockade-dependent cardiac allograft toler

97 ntribution of Tregs to immune suppression by costimulation blockade depends on the concentration of C

98 from diabetes by a short course of combined costimulation blockade, despite the continued diabetogen

99 mice with very severe diabetes treated with costimulation blockade did not reverse diabetes, showing

100 llograft-protective effects of CD40-directed costimulation blockade do not require sCD154 blockade, c

101 Because costimulation blockade does not result in universal tole

102 CD28 and CD40L costimulation blockade during acute infection also dimin

103 rse patient groups, with novel approaches of costimulation blockade (eg, CD154, CD28) advancing towar

104 monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and

105 N-gamma+/+ and IFN-gamma-/- mice, and T-cell costimulation blockade enhanced alloantigen-induced T-ce

106 gld mice treated with costimulation blockade enjoy a significantly greater inc

107 The data also suggest that B7-CD28 T-cell costimulation blockade exerts immunosuppressive actions

108 e almost completely protected from diabetes, costimulation blockade failed to prolong skin allograft

109 Costimulation blockade fails to prolong skin allograft s

110 cy of Th17 cells and conferred resistance to costimulation blockade following transplantation.

111 , n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n =

112 Costimulation blockade has been shown to be effective in

113 T cell costimulation blockade has shown promise as an alternati

114 earts to rapamycin improves the effect of B7 costimulation blockade in prolonging heart allograft sur

115 ne or rapamycin were compared as adjuncts to costimulation blockade in the murine BALB/c to C3H/He he

116 intenance of allograft protection induced by costimulation blockade in this model.

117 d transplantation, where treatments based on costimulation blockade, in particular CD40 ligand (CD40L

118 linated neoantigens and clinical efficacy of costimulation blockade indicate a general defect in main

119 asL is not required for the establishment of costimulation blockade induced hyporesponsiveness, but r

120 Last, the combination of aNotch-1 with costimulation blockade induced long-term tolerance in a

121 D8 T-cell depletion together with CD4 T cell-costimulation blockade induced more robust tolerance.

122 Surprisingly, costimulation blockade induced permanent islet allograft

123 Deletion of CD4 or CD25 cells during costimulation blockade induced rapid rejection of skin b

124 found that IL-10 was not required for early costimulation blockade-induced allograft acceptance.

125 human autoimmune diabetes, are resistant to costimulation blockade-induced allograft tolerance.

126 This study demonstrated that short-term costimulation blockade-induced dominant tolerance and th

127 e role of Foxp3 regulatory T (Treg) cells in costimulation blockade-induced dominant tolerance to por

128 Strain differences in costimulation blockade-induced hyporesponsiveness persis

129 sis that NOD mice would also be resistant to costimulation blockade-induced rat xenograft tolerance.

130 nity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance

131 Costimulation blockade induces prolonged rat islet and s

132 e and rapamycin may provide a means to bring costimulation blockade into the clinic.

133 closporine and rapamycin upon the outcome of costimulation blockade is forwarded.

134 In contrast, costimulation blockade is ineffective in this clinically

135 of NOD mice to resist tolerance induction by costimulation blockade is mediated by both CD4+ and CD8+

136 hematopoietic chimerism in mice treated with costimulation blockade is not known.

137 ft survival in NOD.B6 Idd3 mice treated with costimulation blockade is prolonged compared with NOD mi

138 The alloresponse suppressed by costimulation blockade is restored by LCMV infection and

139 vival in (NOD x C57BL/6)F1 mice treated with costimulation blockade is short, suggesting a strong gen

140 cipients with anti-CD40 ligand and CTLA-4Ig (costimulation blockade) is a powerful promising albeit n

141 After costimulation blockade, islet allograft survival was pro

142 Moreover, short-term costimulation blockade led to robust immune tolerance th

143 er the diagnosis of type 1 diabetes and that costimulation blockade may exert its beneficial therapeu

144 Here we demonstrate that costimulation blockade-mediated tolerance after lung tra

145 hypothesize that CD8(+) T cell "escape" from costimulation blockade might be a IL-15/IL-15R dependent

146 olerance, we hypothesized that "escape" from costimulation blockade might represent a CD8(+) and IL-1

147 In the acute model, treatment with costimulation blockade (MR1/CTLA4-Ig) resulted in attenu

148 s with conventional agents (n=3) or based on costimulation blockade (n=7).

149 In murine models, T-cell costimulation blockade of the CD28:B7 and CD154:CD40 pat

150 Costimulation blockade of the CD40/CD154 pathway has bee

151 erefore, besides direct inhibition of T-cell costimulation, blockade of B7/CD28 may facilitate induct

152 Costimulation blockade or gene knockout of either CD28 o

153 depleting mechanism of action and not merely costimulation blockade plays a substantial role in the t

154 .TNFR2-/- and B6.IL-12R-/- mice treated with costimulation blockade plus LPS also exhibited short ski

155 oncytotoxic, irradiation-free approach using costimulation blockade plus rapamycin treatment.

156 ovide insight into potential risks following costimulation blockade posed by chronic or latent viral

157 Importantly, costimulation blockade prevented the rejection of alloge

158 lycytidylic acid (TLR3) to mice treated with costimulation blockade prevents alloreactive CD8(+) T ce

159 Costimulation blockade prolonged skin allograft survival

160 Although CD154 costimulation blockade prolongs allograft survival in mu

161 Using a costimulation blockade protocol based on a donor-specifi

162 We used a costimulation blockade protocol consisting of a donor-sp

163 Costimulation blockade protocols are effective in prolon

164 indings help define one mechanism by which a costimulation blockade/rapamycin-based therapy following

165 ensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells,

166 ection, recipients treated with a CD28-CD154 costimulation blockade regimen achieved sustained insuli

167 pproaches, but unexpectedly, the efficacy of costimulation blockade requires the presence of a radiat

168 Fas expression is not critical for costimulation blockade resistant rejection, suggesting t

169 but rather appears to be required for normal costimulation blockade resistant rejection.

170 resents a new and potent strategy to prevent costimulation blockade-resistant CD8(+) T cell-driven re

171 IL-6 ablated the Th17 response and reversed costimulation blockade-resistant graft rejection.

172 We have previously shown that the costimulation blockade-resistant phenotype can be attrib

173 in cells of hemopoietic origin and that the costimulation blockade-resistant phenotype is dominant.

174 A-1-specific induction therapy to neutralize costimulation blockade-resistant populations of T cells

175 Costimulation blockade-resistant rejection (CoBRR) is as

176 raft rejection and specifically limits early costimulation blockade-resistant rejection (CoBRR).

177 nfection, but, strikingly, failed to mediate costimulation blockade-resistant rejection after challen

178 To elucidate the mechanisms of costimulation blockade-resistant rejection and to improv

179 he ability of donor-reactive Tmem to mediate costimulation blockade-resistant rejection during a reca

180 is study, we report that CD8(+) Th17 mediate costimulation blockade-resistant rejection in T-bet(-/-)

181 We hypothesize that the costimulation blockade-resistant rejection mediated by L

182 jection, these approaches fail, resulting in costimulation blockade-resistant rejection.

183 ng rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.

184 +) CD8(+) cells play a critical role in this costimulation blockade-resistant rejection.

185 gesting a link between CD28-negative Tem and costimulation blockade-resistant rejection.

186 kthrough response temporally correlated with costimulation blockade-resistant rejection.

187 CD8 T cells are necessary for costimulation blockade-resistant rejection.

188 memory T (TM) cells have been implicated in costimulation blockade-resistant transplant rejection, d

189 To determine whether the costimulation blockade resulted in tolerance, adult-thym

190 When mice were treated with costimulation blockade, reversal of diabetes was observe

191 r of NF-kappa B translocation, together with costimulation blockade, synergistically impairs memory T

192 y) total body irradiation and treatment with costimulation blockade, T-cell depletion, or rapamycin.

193 Costimulation blockade targeting B7, CD40L, or CD11a sig

194 nd support further investigation of combined costimulation blockade targeting the CD28 and CD40 pathw

195 ration occurred in protected recipients, yet costimulation blockade temporarily blunted early T-cell

196 ival of skin allografts in mice treated with costimulation blockade through a CD8 T cell-dependent, M

197 ore, strategies that restrict the effects of costimulation blockade to effector T cells would be adva

198 mpeded transplantation tolerance elicited by costimulation blockade to offspring-matched cardiac graf

199 treatment drastically blunts the ability of costimulation blockade to produce long-term engraftment.

200 cyclosporine therapy blocked the capacity of costimulation blockade to produce permanent engraftment,

201 rlying mechanisms, we studied the ability of costimulation blockade to prolong islet allograft surviv

202 ome the failure of calcineurin inhibitors or costimulation blockade to prolong the survival of major-

203 during rejection compared with isografts or costimulation blockade-treated allografts.

204 ermanent engraftment, combined rapamycin and costimulation blockade treatment produced permanent engr

205 strain combination known to be refractory to costimulation blockade treatment, combined treatment wit

206 , interclonal CD8-CD8 help was suppressed by costimulation blockade treatment.

207 vented in the early posttransplant period by costimulation blockade using CD154 or anti-inducible cos

208 aft tolerance in mice induced through either costimulation blockade using CD154-specific antibody the

209 ipheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion

210 tested whether T(FH) cells were decreased by costimulation blockade using the CTLA-4-immunoglobulin (

211 depletion in (NOD x CBA)F1 mice treated with costimulation blockade was impaired compared with simila

212 When costimulation blockade was introduced in 2000, the adapt

213 eracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the con

214 cy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inh

215 Costimulation blockade with belatacept did not provide s

216 rapamycin inhibitor, everolimus, and T-cell costimulation blockade with belatacept) offer potential

217 We evaluated the combination of costimulation blockade with bortezomib in a sensitized n

218 These data suggest that combining costimulation blockade with IL-2 treatment may selective

219 In this model, donor cell infusion and costimulation blockade without busulfan were insufficien

220 cluding short-term depleting anti-CD4 mAb or costimulation blockade, would affect the disease progres