ライフサイエンスコーパス: CTLA-4

1 cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4).

2 D-1) alone or combined with ipilimumab (anti-CTLA-4).

3 co-blockade of CTLA-4 with ipilimumab (anti-CTLA-4).

4 f HNSCC lesions respond to intratumoral anti-CTLA-4.

5 ree and overall survival in response to anti-CTLA-4.

6 f anti-PD-1/L1 than after resumption of anti-CTLA-4.

7 hways and checkpoints such as PD-1/PD-L1 and CTLA-4.

8 had high levels of PD-1 and coexpression of CTLA-4.

9 eading to sustained upregulation of PD-1 and CTLA-4.

10 including the coinhibitor receptors PD-1 and CTLA-4.

11 rgeting the immunologic checkpoints PD-1 and CTLA-4.

12 , were 8209 per 100 000 for ipilimumab (anti-CTLA-4), 2542 per 100 000 for nivolumab (anti-PD-1), 245

13 nction of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 has shown promise for augm

14 niche relative to areas outside this region (CTLA-4, 38% vs 18% [P = .0001]; CD86, 38% vs 24% [P = .0

15 demonstrate that the active delivery of anti-CTLA-4 (a checkpoint inhibitor drug) results in greatly

16 he latter could be further augmented by anti-CTLA-4 Ab to achieve tumor eradication and immunological

17 28 engagement was blocked, but unaffected by CTLA-4 activation or blockade.

18 sumed an anti-cytotoxic T-cell lymphocyte-4 (CTLA-4) agent, and 135 an anti-programmed cell death 1 o

19 h qualitatively and quantitatively over anti-CTLA-4 alone, and its efficacy depended on CD4 T cells,

20 34%) overall (44% of those receiving an anti-CTLA-4 and 32% of those receiving an anti-PD-1/L1); 47 o

21 checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1.

22 tudies of cancer immunotherapies beyond anti-CTLA-4 and anti-PD(L)1 and discuss how these results are

23 inforces the antitumor activity of both anti-CTLA-4 and anti-PD-1 antibodies.

24 n T cell phenotypes were observed after anti-CTLA-4 and anti-PD-1 antibody blockade.

25 Combination anti-CTLA-4 and anti-PD-1 blockade therapy has enhanced effic

26 Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint-blockade-induced immune

27 d that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tum

28 However, even when using anti-CTLA-4 and anti-PD-1 in combination, approximately half

29 poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1.

30 of glioblastoma multiforme treated with anti-CTLA-4 and anti-PD-1.

31 Immune checkpoint therapy with anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatm

32 it nanomolar affinity to hCD80 and displaced CTLA-4 and CD28 at nanomolar concentrations.

33 gand cis-interaction and its ability to bind CTLA-4 and CD28, but not PD-1, suggests that these pathw

34 d rhesus macaques, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade u

35 the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients ac

36 ipilimumab contacts the front beta-sheet of CTLA-4 and intersects with the CTLA-4:Beta7 recognition

37 r strategy to address DSA via the sparing of CTLA-4 and more potent targeting of Tfh cells.

38 et the T cell inhibitory checkpoint proteins CTLA-4 and PD(L)1 are efficacious across a broad range o

39 Targeting the CTLA-4 and PD-1 "checkpoints" is an effective treatment

40 dies targeting T cell coinhibitory receptors CTLA-4 and PD-1 (programmed death-1) that have shown act

41 lorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade.

42 -blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lun

43 ting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melan

44 dies targeting checkpoint inhibitors such as CTLA-4 and PD-1 have proven to be highly effective for t

45 I polarization, and decreased expression of CTLA-4 and PD-1 in BAL Tregs, suggesting both activation

46 infection, which suggests the importance of CTLA-4 and PD-1 in immune modulation in a chronic helmin

47 herefore, we sought to determine the role of CTLA-4 and PD-1 in regulating CD4(+) and CD8(+) T-cell r

48 Thus, we demonstrate that CTLA-4 and PD-1 limit the induction of particular T-cell

49 imulus, staphylococcal enterotoxin B, Abs to CTLA-4 and PD-1 reversed HIV latency in proliferating an

50 hese findings indicate that dual blockade of CTLA-4 and PD-1 therapy is sufficient to induce unique c

51 ells contain high levels of cells expressing CTLA-4 and PD-1, as well as amounts of cell-associated S

52 ese monoclonal antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors on ac

53 ess of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear ident

54 eries that converge mainly on two molecules, CTLA-4 and PD-1, that were recognized with the 2018 Nobe

55 ells that express the coinhibitory receptors CTLA-4 and PD-1, two subsets previously shown to be enri

56 nce of the negative co-stimulatory molecules CTLA-4 and PD-1.

57 ritical immunoregulatory pathways, including CTLA-4 and PD-1.

58 rapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer

59 t-in-class immunotherapeutic for blockade of CTLA-4 and significantly benefits overall survival of pa

60 LA-4) and programmed cell death 1 (PD-1), or CTLA-4 and the PD-1 ligand (PD-L1) exhibits superior ant

61 easing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical nee

62 T-cell exhaustion (CD8(+ )PD-1(+)/CTLA-4(+)) and treatment-induced depletion of regulatory

63 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and CD80.

64 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially rev

65 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1), or CTLA-4 an

66 cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to su

67 cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) have

68 totoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely

69 es such as cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1).

70 cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), which dampen effe

71 cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor 1 (PD-1) were inef

72 XCL10 were positively correlated with PDCD1, CTLA-4, and CD8(+) T-cell subset, but negatively correla

73 The family includes CD28, CTLA-4, and ICOS as well as other proteins, including PD

74 Immunotherapy targeting PD-1, CTLA-4, and IL-27 blocked CD4(+) T cell exhaustion durin

75 lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) c

76 ichment of ICOS, CD45RO, PD-1, PDL-1, LAG-3, CTLA-4, and TIM-3 on BLIMP-1(+) Tregs suggests that BLIM

77 hension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection.

78 though combination checkpoint blockade (anti-CTLA-4 + anti-PD-1) was ineffective against BRAFi-resist

79 uding anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-pr

80 However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Delta-mIL12 cured most mice in

81 sed to modulate the clinical outcome of anti-CTLA-4 antibodies and possibly other antibody-based immu

82 However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high t

83 176b enhances the antitumor activity of anti-CTLA-4 antibodies through mechanisms involving caspase-1

84 therapeutically separable activities of anti-CTLA-4 antibodies.

85 Immune checkpoint inhibitors such as anti-CTLA-4 antibody are widely accepted therapeutic options

86 oenvironment and increasing efficacy of anti-CTLA-4 antibody in the combination treatment.

87 ligand Pam3CSK4 plus i.p. injections of anti-CTLA-4 antibody.

88 notherapy, in particular treatment with anti-CTLA-4 antibody.

89 CD28 and CTLA-4 are major costimulatory and coinhibitory cell sur

90 CD28 and CTLA-4 are members of a family of immunoglobulin-related

91 int inhibitors, which target PD-1, PD-L1 and CTLA-4, are increasingly used for certain cancers; howev

92 w therapeutic targets beyond PD-1, PD-L1 and CTLA-4, as well as new combination approaches.

93 uring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target

94 afficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockou

95 n immunostimulatory effect by repressing the CTLA-4 axis; this has implications to the synergy of ant

96 cytotoxic T lymphocyte-associated protein 4 (CTLA-4):B7-1 are among the most important immune checkpo

97 kpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are no

98 beta-sheet of CTLA-4 and intersects with the CTLA-4:Beta7 recognition surface, indicating that direct

99 enabled us to specifically deplete K3 with a CTLA-4-binding RNA aptamer linked to a K3-siRNA (small i

100 CTLA-4 blockade augments HIV-1 Env antibody responses in

101 CTLA-4 blockade enhanced the humoral alloresponse and, i

102 In a Friend retrovirus infection model, CTLA-4 blockade in particular was able to improve contro

103 olyI:C and CpG was superior to combined PD-1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb

104 CTLA-4 blockade increased IFN-gamma and CD40L production

105 PD-1/CTLA-4 blockade increased the proportion of HCV-specific

106 Because CTLA-4 blockade leads to proliferation of circulating T

107 The clinical benefit of CTLA-4 blockade on T cells is known, yet the impact of i

108 Here, we review these 2 diseases and CTLA-4 blockade therapy, emphasizing the crucial role of

109 refractory to PD-1 blockade may benefit from CTLA-4 blockade.

110 ultured CD80(+) cells, with restoration upon CTLA-4 blockade.

111 mours when used in combination with systemic CTLA-4 blockade.

112 s-I antigens in the presence/absence of PD-1/CTLA-4 blockade.

113 caques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germ

114 These results indicate that the silencing of CTLA-4 can potentiate the T cell priming capacity of the

115 miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis.

116 These results implicate CTLA-4:CD86 interactions as a component of the immunolog

117 R-214 in combination with anti-PD-1 and anti-CTLA-4 checkpoint blockade therapy or peptide-based vacc

118 one should preserve rather than inhibit the CTLA-4 checkpoint while enhancing the efficacy and selec

119 ormer is attributable to inactivation of the CTLA-4 checkpoint, while the latter is due to selective

120 D-1 alone (sICB) or in combination with anti-CTLA-4 (cICB).

121 Coculture of T cells with CTLA-4(+) CLL cells decreased IL-2 production.

122 Coculture of CTLA-4(+) CLL cells with CD80-GFP(+) cell lines revealed

123 CLL cells, among other cancer cells, are CTLA-4(+) Coculture with activated human T cells induced

124 CTLA-4-Ig blocks both CD28 costimulation and CTLA-4 coinhibition.

125 erent requirements in CD28 costimulatory and CTLA-4 coinhibitory signals to control naive and memory

126 ations to the synergy of anti-PD-L1 and anti-CTLA-4 combination therapy.

127 molecules, including Foxp3, CD25, Nrp-1 and CTLA-4, coupled with a loss of Treg suppressive function

128 t model, and this tolerance was dependent on CTLA-4 (cytotoxic T-lymphocyte-associated antigen-4) sig

129 mma, IFNalpha, interleukin-2, interleukin-7, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), T-

130 Heterozygous CTLA-4 deficiency has been reported as a monogenic cause

131 de, and conversely to treat autoimmunity and CTLA-4 deficiency.

132 This CTLA-4-dependent inhibition was Tfh cell specific in tha

133 r cells and antigen presenting cells (APCs), CTLA-4 expressed on the breast cancer cells bind to CD80

134 erleukin-2 (IL-2) responsiveness, diminished CTLA-4 expression and increased SATB1 expression.

135 ent inhibition was Tfh cell specific in that CTLA-4 expression by Tfh cells was necessary and suffici

136 Assessing total CTLA-4 expression levels was found to be optimal when re

137 PD-1 and CTLA-4 expression was significantly markedly reduced in

138 ciated with significantly decreased LRBA and CTLA-4 expression with T-cell activation.

139 nued to drive T cell activation and PD-1 and CTLA-4 expression, and blocked T cell differentiation, u

140 ecently reported for LRBA, indirectly affect CTLA-4 expression, resulting in clinically similar disor

141 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression levels.

142 cytotoxic T lymphocyte-associated protein 4 (CTLA-4) for cancer immunotherapy, a large number of pati

143 lysosomal-blocking compounds, distinguished CTLA-4 from LRBA mutations.

144 e PD-1 pathway, PD-L1, affects both PD-1 and CTLA-4 function, raising new questions about the biologi

145 the primary driver of Treg proliferation and CTLA-4 functions as the main brake but is likely depende

146 o, resulted in the development of belatacept CTLA-4 fused with an immunoglobulin Fc domain, a biologi

147 it compared with all other treatments except CTLA-4/granulocyte macrophage colony-stimulating factor.

148 Thus selective CD28 blockade that spares CTLA-4 has potential to result in improved inhibition of

149 tory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, no

150 The latter was largely confined to CTLA-4(hi)-expressing FOXP3(hi)-enriched CD25(hi)CD4 T c

151 oint blockade regimens targeting PD-1 and/or CTLA-4, if performed in people living with HIV with sust

152 One of the patients has been treated with CTLA-4-Ig and achieved sustained remission.

153 l for the inhibition of alloimmunity in that CTLA-4-Ig blocks both CD28 costimulation and CTLA-4 coin

154 Abatacept is a CTLA-4-Ig fusion protein that binds to the costimulatory

155 CD28 blockade with CTLA-4-Ig has the ability to reduce the incidence of the

156 anti-CD28 domain antibody (dAb) compared to CTLA-4-Ig led to superior inhibition of Tfh cell, germin

157 Blockade of CD80/CD86 with CTLA-4-Ig markedly reduced the cycling and absolute numb

158 ells that was reversed upon cotreatment with CTLA-4-Ig.

159 h the emergence of an anergic and regulatory CTLA-4(+)IL-2(low)Foxp3(-) T cell population, where the

160 PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell acti

161 PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) immune checkpoints led to a series of clinical t

162 tration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed

163 ecreased by costimulation blockade using the CTLA-4-immunoglobulin (Ig) fusion protein (abatacept) in

164 el of anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy of colon cancer.

165 CTLA-4 imposes major boundaries on CD4(+) T cell phenoty

166 These data implicate tumor CTLA-4 in cancer cell-mediated immunosuppression in vitr

167 We examined the roles of CD28 and CTLA-4 in driving the activation of thymic resident NKT

168 ade therapy, emphasizing the crucial role of CTLA-4 in immune checkpoint regulation.

169 amenable functional role for Treg cells and CTLA-4 in limiting antimalarial immunity.

170 mplex with the checkpoint inhibitory protein CTLA-4 in regulatory T cells (Tregs).

171 istic expression patterns of CD25, Foxp3 and CTLA-4 in T(reg) cells were fully or partially rescued b

172 umors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhib

173 Targeting Treg cells or CTLA-4 in this precise window accelerated parasite clear

174 th inhibition of immune checkpoints PD-1 and CTLA-4, induced complete and durable regressions (>1 yea

175 In contrast, anti-CTLA-4 induces the expansion of an ICOS(+) Th1-like CD4

176 CTLA-4 induction following stimulation, and the use of l

177 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metasta

178 ic agents, EGFR inhibitors, mTOR inhibitors, CTLA-4 inhibitors, or PD-1/PD-L1 inhibitors, etc.

179 consistent with the known safety profile of CTLA-4 inhibitors.

180 de with antibodies specific for the PD-1 and CTLA-4 inhibitory receptors can induce durable responses

181 xamined the differential effects of CD28 and CTLA-4 interaction with CD80/CD86, as well as MHC class

182 ut significantly lower than that of the B7-1/CTLA-4 interaction, suggesting a distinct basis for PD-1

183 erization inhibited both PD-L1:PD-1 and CD80:CTLA-4 interactions through distinct mechanisms but pres

184 To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy

185 CTLA-4 is a key molecule in immunosuppression, and CD80

186 intensive regimens, suggesting that blocking CTLA-4 is deleterious.

187 Using a human CTLA-4 knock-in mouse lacking FcgammaR function, antitum

188 ed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently

189 ibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and

190 nd that unlike other coinhibitory molecules (CTLA-4, LAG-3, TIM-3), PD-1 was highly expressed by subd

191 Direct mutation in CTLA-4 leads to defective regulatory T-cell (Treg) funct

192 scence readouts, we found that PD-L1 and the CTLA-4 ligand CD80 heterodimerize in cis but not trans.

193 , and a subset of TAMs, are positive for the CTLA-4 ligand CD86 and that the fractions of T cells and

194 Hui et al. reveal that interaction between a CTLA-4 ligand, CD80, and its counterpart in the PD-1 pat

195 th impaired ability to control levels of the CTLA-4 ligands, CD80 and CD86.

196 uppressed proliferation more weakly than did CTLA-4(lo/-)CD25(hi)FOXP3(hi)-enriched T cells.

197 ked to a K3-siRNA (small interfering RNA) in CTLA-4(+) LSCs in vivo, which mobilized LSCs in the BM,

198 Treatment with anti-CTLA-4 mAb altered MP Treg and MP CD4(+) and CD8(+) T ce

199 expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tu

200 suggesting a distinct basis for PD-1- versus CTLA-4-mediated inhibition.

201 eloped on the rationale that preservation of CTLA-4-mediated regulatory mechanisms would result in a

202 on antigen-presenting cells (APCs) prevented CTLA-4-mediated trans-endocytosis of CD80.

203 nable personalized therapy with abatacept, a CTLA-4 mimetic, and inform genetic counseling.

204 y, we intended to suppress the expression of CTLA-4 molecule on tumor-infiltrating T cells by siRNA-l

205 s, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecules are one of the main barriers in primin

206 cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients wit

207 ell-based binding assay against a library of CTLA-4 mutants and by direct biochemical approaches.

208 rapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57).

209 CTLA-4 on CLL-derived human cell lines decreased CD80 ex

210 CD86 interacted with the receptors CD28 and CTLA-4 on neighboring T cells; these interactions fed tw

211 with activated human T cells induced surface CTLA-4 on primary human CLL B cells.

212 r -bearing mice led to the downregulation of CTLA-4 on tumor -infiltrating T cells, which was associa

213 mor efficacy was observed by blocking murine CTLA-4 on tumor cells in isolation of the T cell effect

214 cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CD4(+) T cells of albendazole-treated individ

215 cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CML-LSCs but not normal hematopoietic stem ce

216 In contrast, induction of IDO1 using CTLA-4 or a TLR-3 ligand dampened proinflammatory respon

217 ta-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB an

218 phenotypic profile in mice treated with anti-CTLA-4 or anti-PD-1 immunotherapy, whereas their periphe

219 A total of 3123 patients who received anti-CTLA-4 or anti-programmed cell death 1 (PD-1) therapy we

220 Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can

221 Our data reveal that CTLA-4 or PD-1 blockade results in significantly enhance

222 s stimulated with parasite antigen following CTLA-4 or PD-1 blockade.

223 Ipilimumab (anti-CTLA-4) or anti-PD-1/PD-L1 monotherapy failed to show a

224 ssing PD-1, TIM-3, CTL-associated protein 4 (CTLA-4), or B and T lymphocyte attenuator (BTLA).

225 cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] or programmed cell death 1 [PD-1]) inhibitor.

226 yping approaches sensitive to defects in the CTLA-4 pathway are therefore required to inform understa

227 Here, we focus on the biology of the CD28/CTLA-4 pathway as a framework for understanding the impa

228 s appropriate for testing novel mutations in CTLA-4 pathway genes.

229 functional significance of mutations in the CTLA-4 pathway identified by gene-sequencing approaches.

230 t antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotrans

231 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential

232 However, additional mutations affecting the CTLA-4 pathway, such as those recently reported for LRBA

233 f distinguishing a variety of defects in the CTLA-4 pathway.

234 contrast to PD-1(+) Tfh cells, SIV-enriched CTLA-4(+)PD-1(-) CD4(+) T cells were found outside the B

235 We have shown that CTLA-4(+)PD-1(-) memory CD4(+) T cells are a previously

236 , SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phen

237 mune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1.

238 s targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vacci

239 ics targeting the inhibitory receptors (IRs) CTLA-4, PD-1 or PD-L1 have made substantial clinical pro

240 increased expression of coinhibitory factors CTLA-4, PD-1, and Blimp-1, and decreased expression of c

241 imulatory (CD28, ICOS) and inhibitory roles (CTLA-4, PD-1, BTLA, and TIGIT) in T-cell function.

242 the immune-regulatory "checkpoint" receptors CTLA-4, PD-1, or its ligand PD-L1, can produce durable r

243 ne previous systemic therapy (excluding anti-CTLA-4, PD-1, or PD-L1 agents).

244 ta-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly exte

245 Thus, despite CTLA-4/PD-1 blockade inducing robust latency reversal an

246 In lymph nodes, dual CTLA-4/PD-1 blockade, but not PD-1 alone, decreased the

247 s, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade using monoclonal

248 ll responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targ

249 the largest trial to date in mCRPC with anti-CTLA-4 plus anti-PD-1 (nivolumab 1 mg/kg plus ipilimumab

250 ulations to monotherapy and combination anti-CTLA-4 plus anti-PD-1 therapy in syngeneic murine tumors

251 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-positive T cells (compared with reactive lymphoi

252 t the fractions of T cells and TAMs that are CTLA-4-positive and CD86-positive, respectively, are gre

253 Importantly, CTLA-4-positive cells are present, and focally contact H

254 criptional inhibitor that directly bound the CTLA-4 promoter and regulated its activity.

255 424-3p and immunohistochemistry was used for CTLA-4 protein detection.

256 vels of cytotoxic T-lymphocyte-associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral

257 d blocks their interaction with the CD28 and CTLA-4 receptors expressed by T cells, therefore inhibit

258 bined treatment with anti-CD40/CpG + IC/anti-CTLA-4 reduced T regulatory cells in the tumors and was

259 e selectivity exhibited by ipilimumab toward CTLA-4 relative to the homologous and functionally relat

260 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes

261 cytotoxic T lymphocyte-associated protein 4 (CTLA-4) restored antitumor immunity in miR-155 T cell-co

262 le combination of ISF35, anti-PD-1, and anti-CTLA-4 results in complete eradication of injected and n

263 t a combination of anti-CD40/CpG and IC/anti-CTLA-4 should be developed for clinical testing as a pot

264 cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune

265 Moreover, the administration of anti-CTLA-4 siRNA-loaded NPs into CT26 and 4 T1 tumor -bearin

266 tient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced funct

267 Anti-CD40/CpG + IC/anti-CTLA-4 synergistically induced regression of advanced s.

268 of CD80-GFP into CLL tumor cells, similar to CTLA-4(+) T cells able to trans-endocytose CD80.

269 complex formed by ipilimumab with its human CTLA-4 target.

270 e we argue that for safer and more effective CTLA-4-targeting immune therapy, one should preserve rat

271 CTLA-4-targeting immunotherapy was the first example tha

272 t typical suppressive factors such as PD-L1, CTLA-4, TGF-beta, IL-35, and IL-10, contributes to apopt

273 g HRS cells are more frequently positive for CTLA-4 than for PD-1 or LAG-3.

274 ilimumab is a fully human antibody targeting CTLA-4 that received FDA approval for the treatment of m

275 gene encoding the immunomodulatory receptor CTLA-4 that was associated with resistance to autoimmuni

276 initially high expression levels of PD-1 and CTLA-4 that were associated with negative regulation of

277 D-1/L1 therapy than after resumption of anti-CTLA-4 therapy (OR, 0.30; 95% CI, 0.11 to 0.81; P = .019

278 Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the

279 umours when combined with anti-PD-1 and anti-CTLA-4 therapy.

280 s associated with primary resistance to anti-CTLA-4 therapy.

281 anoma model refractory to anti-PD-1 and anti-CTLA-4 therapy.

282 oxin B, only the combination of Abs to PD-1, CTLA-4, TIM-3, and TIGIT reversed latency.

283 Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable th

284 Our model predicts survival in anti-CTLA-4-treated patients with melanoma and anti-PD-1-trea

285 420 ) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients,

286 n immunosuppressive role for tumor-expressed CTLA-4 using chronic lymphocytic leukemia (CLL) as a dis

287 ant DEF6 to RAB11 as well as reduced RAB11(+)CTLA-4(+) vesicles in DEF6-mutated cells.

288 ire T cells, the antitumor effect of IC/anti-CTLA-4 was dependent on T cells.

289 paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after

290 etion of regulatory T-cells (CD4(+) Foxp3(+)/CTLA-4(+)) was seen in tumor or blood in 5/5 patients wi

291 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine ex

292 d by breast cancer cells and transmitted via CTLA-4 were sufficiently strong to displace CD80 from th

293 PD-1 and CTLA-4 were upregulated on tumor-infiltrating CD4(+) and

294 cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which limit T cell activation via synergistic m

295 letion with the immunotherapeutic agent anti-CTLA-4, which dramatically increased the frequency and d

296 orientated assay to measure ligand uptake by CTLA-4, which is sensitive to ligand-binding or -traffic

297 neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients

298 ence of other exhaustion markers; inhibiting CTLA-4 with a nondepleting antibody overcame the CD8(+)

299 ogic inhibiting interaction of both CD28 and CTLA-4 with CD80/86.

300 nd this effect was negated by co-blockade of CTLA-4 with ipilimumab (anti-CTLA-4).