GENETICS AND MECHANISMS OF DLI EFFECTS FOLLOWING NON-MYELOBLATIVE HCT
非清髓性 HCT 后 DLI 效应的遗传学和机制
基本信息
- 批准号:7158094
- 负责人:
- 金额:$ 29.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:antineoplasticsantitumor antibodybioengineering /biomedical engineeringcell linecell migrationcell proliferationclinical researchgraft versus host diseasehematopoietic tissue transplantationhomologous transplantationhybrid antibodyinflammationinjection /infusionleukemialeukocyte activation /transformationlymphocytelymphomaminiature swinemodel design /developmentmolecular dynamicsneoplasm /cancer radiation therapyneoplastic cellnonhuman therapy evaluationstem cell transplantationtissue donorstransfection
项目摘要
Non-myeloablative hematopoietic cell transplantation (HCT) followed by delayed donor leukocyte infusion
(DLI) is a promising immunotherapeutic approach to treat hematologic malignancies including leukemias and
lymphomas. Major limitations of this approach, however, include the risks of graft failure, graft-versus-host
disease, (GVHD) and infection. MGH MHC-inbred miniature swine provide a pre-clinical model for studies of
transplantation biology with responses to HCT resembling those of humans. Preliminary data suggest that a
novel, minimally myelosuppressive preparative regimen leads to stable multilineage chimerism following highdose
haploidentical HCT, without causing GVHD. In this proposal we aim to 1) determine the immunological
mechanisms involved in controlling hbst-versus-graft (HVG) and GVH responses that allow engraftment
without GVHD across MHC barriers in this model. These studies will be performed in close collaboration with
Projects 1 and 2 to extend the mechanistic studies in rodent models. We will then 2) optimize the swine
model to facilitate translation of this protocol to the clinic and analyze the importance of specific genetic
disparities (haploidentical class I and II, class I only, class II only) on engraftment, GVHD and the effects of
subsequent DLI. In collaboration with Project 4, we will test novel strategies to improve stem cell harvests
following cytokine mobilization through parathyroid hormone (PTH) stimulation. Increased numbers of stem
cells in the leukapheresis product following PTH stimulation and cytokine mobilization may enable stable
engraftment using lower doses of cells more easily attainable in the clinic. It is hoped that results of these
studies will permit the development of tailored approaches to the use of DLI in chimeric patients depending
on their HLA disparities from the donor. In addition, we plan to 3) further develop the swine model to allow
direct assessment of graft-versus-tumor effects of HCT and DLI. For this purpose, we will establish tumor cell
lines derived from inbred miniature swine and adapt these tumor lines for in vivo growth in pigs. With the
recent availability of histocompatible miniature swine, and tumor lines derived from these highly inbred
animals, we have the unique opportunity to develop transplantable tumors in a preclinical large animal model.
These studies could provide a foundation for future immunotherapeutic approaches for the treatment of
hematological malignancies that may be translated toward treatment of human disease.
非清髓性造血细胞移植(HCT)后延迟供体白细胞输注
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID H SACHS其他文献
DAVID H SACHS的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID H SACHS', 18)}}的其他基金
Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure
猪胰岛-肾复合异种移植治疗糖尿病和肾衰竭
- 批准号:
10019062 - 财政年份:2020
- 资助金额:
$ 29.93万 - 项目类别:
Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure
猪胰岛-肾复合异种移植治疗糖尿病和肾衰竭
- 批准号:
10395586 - 财政年份:2020
- 资助金额:
$ 29.93万 - 项目类别:
Composite porcine islet-kidney xenotransplants to cure diabetes and renal failure
猪胰岛-肾复合异种移植治疗糖尿病和肾衰竭
- 批准号:
10597990 - 财政年份:2020
- 资助金额:
$ 29.93万 - 项目类别:
Tolerance Induction in a GalT-KO Pig-to-Baboon Model Through Mixed Chimerism
通过混合嵌合现象在 GalT-KO 猪狒狒模型中诱导耐受
- 批准号:
8190115 - 财政年份:2011
- 资助金额:
$ 29.93万 - 项目类别:
Thymic Rejuvenation for the Induction of Transplantation Tolerance
胸腺复兴诱导移植耐受
- 批准号:
8206651 - 财政年份:2010
- 资助金额:
$ 29.93万 - 项目类别:
Thymic Rejuvenation for the Induction of Transplantation Tolerance
胸腺复兴诱导移植耐受
- 批准号:
8011723 - 财政年份:2010
- 资助金额:
$ 29.93万 - 项目类别:
Thymic Rejuvenation for the Induction of Transplantation Tolerance
胸腺复兴诱导移植耐受
- 批准号:
8417615 - 财政年份:2010
- 资助金额:
$ 29.93万 - 项目类别:
Thymic Rejuvenation for the Induction of Transplantation Tolerance
胸腺复兴诱导移植耐受
- 批准号:
7768244 - 财政年份:2010
- 资助金额:
$ 29.93万 - 项目类别:
TOLERANCE TO VASCULARIZED ALLOGRAFTS IN MINISWINE
小型猪对血管化同种异体移植物的耐受性
- 批准号:
7922284 - 财政年份:2009
- 资助金额:
$ 29.93万 - 项目类别:
相似海外基金
Tumor Diagnosis and Therapy in Nuclear Medicine Using Radioactive Technetium and Rhenium Labeled Antitumor Antibody.
使用放射性锝和铼标记的抗肿瘤抗体进行核医学肿瘤诊断和治疗。
- 批准号:
01470143 - 财政年份:1989
- 资助金额:
$ 29.93万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Usefulness of radioimmunodetection and radioimmunotherapy with polymonoclonal antitumor antibody using melanoma bearing mice.
使用携带黑色素瘤的小鼠进行放射免疫检测和使用多单克隆抗肿瘤抗体进行放射免疫治疗的有用性。
- 批准号:
63570498 - 财政年份:1988
- 资助金额:
$ 29.93万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)