更新于：2024-11-21

Allotrap 07

更新于：2024-11-21

概要

研发状态

概要

基本信息

药物类型

合成多肽

别名

靶点-

作用机制

细胞毒性T淋巴细胞抑制剂

治疗领域

免疫系统疾病

在研适应症-

非在研适应症

器官移植排斥

原研机构

SangStat Medical Corp.

在研机构-

非在研机构

Atos SESangStat Medical Corp.

最高研发阶段终止临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C53H90N20O16

InChIKeyKXASYRUYKYOKGG-IWLMWFOOSA-N

CAS号151232-75-6

序列信息

Sequence Code 14639764

关联

100 项与 Allotrap 07 相关的临床结果

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100 项与 Allotrap 07 相关的转化医学

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100 项与 Allotrap 07 相关的专利（医药）

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项与 Allotrap 07 相关的文献（医药）

1998-01-01·The Annals of Thoracic Surgery2区 · 医学

Induction of Tolerance in Rodent Cardiac Allotransplantation Using an MHC Class I-Derived Peptide and Cyclosporin A

2区 · 医学

Article

作者: Roland Buelow ; Saqib Masroor ; John H Artrip ; Oktavijan P Minanov ; Silviu Itescu ; Robert E Michler

BACKGROUNDThe synthetic peptide corresponding to residues 75-84 of the human major histocompatibility complex class I molecule HLA-B7 (Allotrap 07) has been shown to inhibit differentiation of cytotoxic T lymphocyte precursors. Subsequent treatment of LEW-1A rats with this peptide was associated with a reduction in the level of cytotoxic activity directed to donor alloantigens. This study was undertaken to investigate the effect of Allotrap 07 on rodent heart allograft survival in LEW-1A recipients.METHODSHeart allografts from Lewis rats were heterotopically transplanted into the infrarenal abdominal aorta of ACI recipients. The treatment groups consisted of different regimens of short-term intravenous Allotrap 07 and oral cyclosporin A. All grafts were palpated daily, with rejection defined as the cessation of palpable contractions.RESULTSCardiac allografts transplanted from Lewis to ACI rats survived indefinitely after administration of intravenous Allotrap 07 and oral cyclosporin A. Tolerance induction was donor-specific because third-party Brown-Norway, but not Lewis, grafts were rapidly rejected after implantation into ACI recipients.CONCLUSIONSBecause donor-specific tolerance persisted long after cessation of peptide administration and did not occur when cyclosporin A was omitted from the immunosuppressive regimen, the mechanism may involve induction of clonal anergy.

1997-03-01·Journal of Pediatric Surgery3区 · 医学

Treatment with an HLA-peptide and cyclosporine a prolongs rat small bowel allograft surgival

3区 · 医学

Article

作者: M.J Dallman ; P.J Morris ; I.E Willetts ; P.K.H Tam

BACKGROUNDThe ultimate treatment for severe short bowel syndrome is small bowel transplantation (SBT). Current immunosuppression for SBT is relatively ineffective and toxic. Peptides derived from residues 75-84 of the HLA-B7 molecule are immunomodulatory in vitro, and in rodents, when combined with subtherapeutic doses of cyclosporine (CsA), prolong cardiac and skin allograft survival without altering the recipient's rejection kinetics to third party allografts. We investigated the effects of HLA-B7 peptide fragment in a rat model of SBT.METHODSHeterotopic allogeneic SBT was performed in Dagouti (RT1a) to Lewis (RT1l) high-responder rat strain combination. B7.75-84 (40 mg/kg/d) and subtherapeutic CsA (10 mg/kg/d) were administered alone, or in combination, by gavage to allograft recipients on days 0 to 4 after SBT. Recipient pretreatment with B7.75-84 on days -14, -12, -10, and -7 followed by subtherapeutic CsA on days 0 to 4 after SBT was also carried out. Graft rejection was determined by the presence of a palpable abdominal mass on daily examination or by loss of more than 10% initial body weight.RESULTSWithout immunosuppression allografts rejected at a median time of 6 days (range, 5 to 7; n = 7). This was not significantly altered with either CsA therapy alone (median 6 days; range, 6 to 7; n = 6) or B7.75-84 alone (median, 5 days; range, 5 to 6; n = 6). Recipient combination therapy with B7.75-84 and CsA after allografting significantly prolonged allograft survival (median, 11 days; range, 9 to 13; n = 9), as did recipient B7.75-84 pretransplant therapy (median, 10 days; range, 9 to 12; n = 6), when administered over a 2-week period before allografting.CONCLUSIONPost-SBT recipient treatment with B7.75-84 produced statistically significant improvement in allograft survival only after combination with subtherapeutic CsA. Recipient pre-SBT treatment with B7.75-84 alone however, resulted in statistically significant improvement in allograft survival in combination with post-SBT subtherapeutic CsA. These synergistic effects may be valuable in achieving improved SBT survival clinically and warrant further exploration.

1996-04-01·Transplantation2区 · 医学

IMMUNOSUPPRESSIVE EFFECTS OF AN HLA CLASS I-DERIVED PEPTIDE IN A RAT CARDIAC ALLOGRAFT MODEL

2区 · 医学

Article

作者: Buelow, Roland ; Geissler, Edward K. ; Knechtle, Stuart J. ; Fechner, John H. Jr. ; Wang, Jue ; Hanaway, Michael J.

B7.75-84, a 10-amino-acid peptide derived from the HLA-B7 molecule, prolongs rat heterotopic cardiac allograft survival time (GST) when used with cyclosporine in the Lewis-to-ACI strain combination. We evaluated the ability of B7.75-84 to prolong GST in other strain combinations without cyclosporine and studied the effect of B7.75-84 on the immune response in the Wistar-Furth (WF)-to-ACI strain combination. GST was markedly prolonged in most low-responder (ACI) recipients but only slightly prolonged in the high-responder (Lewis) recipient. Cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) limiting dilution assays (LDA) were performed 10 days after cardiac allografts from WF donors were placed in ACI recipients treated with B7.75-84. HTL-LDA assays at 10 days posttransplant showed a slight decrease in HTL precursor frequency and a decrease in their IL-2 production in B7.75-84 treated recipients with prolonged GST in response to donor antigen as well as third-party (Lewis) antigen. CTL-LDA assays at day 10 showed no difference in CTL precursor frequency among treated recipients but did show a significant decrease in CTL killing activity against donor cells in recipients with prolonged GST. No significant difference in CTL killing activity was seen against third- party cells. Antibody analysis was performed at day 8 in treated recipients. Serum from B7.75-84-treated recipients with prolonged graft survival generally showed no detectable IgG antibody response against donor MHC class I antigen. All B7.75-84 treated recipients showed a strong IgM response against donor antigen regardless of allograft outcome. Our results suggest that the immunosuppressive effect of B7.75-84 in rats is greater using a low-responder RT1 haplotype. Furthermore, B7.75-84 induces a nonspecific decrease in HTL function while producing a donor-specific decrease in CTL function and a diminished antidonor MHC class I IgG response.

100 项与 Allotrap 07 相关的药物交易

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