Immune manipulation to generate tumor immunity and regulate GVHD after allogeneic HCT

同种异体 HCT 后通过免疫操作产生肿瘤免疫并调节 GVHD

基本信息

批准号：
10218089
负责人：
Robert Jon Soiffer
金额：
$ 61.28万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-14 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10218089
关键词：
AML/MDS Address Adoptive Cell Transfers Adoptive Immunotherapy Allogenic Antigen-Antibody Complex Antigens Autologous B-Lymphocytes Biological Cell Therapy Cells Clinical Clinical Research Clinical Trials Consent Disease Disease remission Dose Double-Blind Method Engineering FDA approved Face Failure GVAX Cancer Vaccine Genetic Engineering Genomics Granulocyte-Macrophage Colony-Stimulating Factor Hematologic Neoplasms Immune Immune Targeting Immune response Immune system Immunologics Infection Interleukin-2 Intervention Trial Investigation Laboratories Lead Learning Leukemic Cell Life Life Style Lymphocyte Malignant Neoplasms Manipulative Therapies Minor Histocompatibility Antigens Morbidity - disease rate Myeloid Leukemia Myeloproliferative disease Outcome Pathway interactions Patient-Focused Outcomes Patients Peptide Vaccines Phase Phase I/II Trial Placebos Population Prevention Prophylactic treatment Provider Reaction Recurrence Recurrent disease Refractory Regimen Regulatory T-Lymphocyte Relapse Reporting Research Residual Tumors Residual state Risk Safety Series Steroids Supportive care Systemic disease Testing Tissues Toxic effect Transplant Recipients Transplantation Tumor Immunity Vaccines Whole Cell Vaccine base checkpoint inhibition chronic graft versus host disease clinical trial implementation combinatorial design disorder risk efficacy testing experience graft vs host disease hematopoietic cell transplantation high risk immune checkpoint blockade immunoregulation improved improved outcome ipilimumab leukemia mortality neoantigens neoplastic cell novel novel strategies phase I trial prevent prophylactic prospective randomized placebo controlled trial randomized trial relapse patients relapse risk tumor

AML/MDS Address Adoptive Cell Transfers Adoptive Immunotherapy Allogenic Antigen-Antibody Complex Antigens Autologous B-Lymphocytes Biological Cell Therapy Cells Clinical Clinical Research Clinical Trials Consent Disease Disease remission Dose Double-Blind Method Engineering FDA approved Face Failure GVAX Cancer Vaccine Genetic Engineering Genomics Granulocyte-Macrophage Colony-Stimulating Factor Hematologic Neoplasms Immune Immune Targeting Immune response Immune system Immunologics Infection Interleukin-2 Intervention Trial Investigation Laboratories Lead Learning Leukemic Cell Life Life Style Lymphocyte Malignant Neoplasms Manipulative Therapies Minor Histocompatibility Antigens Morbidity - disease rate Myeloid Leukemia Myeloproliferative disease Outcome Pathway interactions Patient-Focused Outcomes Patients Peptide Vaccines Phase Phase I/II Trial Placebos Population Prevention Prophylactic treatment Provider Reaction Recurrence Recurrent disease Refractory Regimen Regulatory T-Lymphocyte Relapse Reporting Research Residual Tumors Residual state Risk Safety Series Steroids Supportive care Systemic disease Testing Tissues Toxic effect Transplant Recipients Transplantation Tumor Immunity Vaccines Whole Cell Vaccine base checkpoint inhibition chronic graft versus host disease clinical trial implementation combinatorial design disorder risk efficacy testing experience graft vs host disease hematopoietic cell transplantation high risk immune checkpoint blockade immunoregulation improved improved outcome ipilimumab leukemia mortality neoantigens neoplastic cell novel novel strategies phase I trial prevent prophylactic prospective randomized placebo controlled trial randomized trial relapse patients relapse risk tumor

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项目摘要

Project Summary Disease relapse and graft versus host disease (GVHD) continue to be major obstacles to improving outcomes for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation. Project 1 will develop and implement a series of novel clinical trials to address these issues in 3 Specific Aims. Aim 1 focuses on immune based strategies to prevent relapse for patients with myeloid malignancies undergoing HCT. These include clinical studies to examine the safety and impact of checkpoint blockade with ipilumumab administered early after allo-HCT in patients with myeloid malignancies at high risk of relapse based on genomic profiling prior to transplant. We will also complete a prospective phase 2 placebo controlled randomized trial of autologous leukemia cell vaccines genetically engineered to secrete GM-CSF (GVAX) administered prophylactically to patients with myeloid leukemias entering allo-HCT with active disease. A third trial will evaluate the impact of novel personal peptide vaccines after HCT designed to target leukemia-specific neoantigens and minor histocompatibility antigens based on genomic characterization of recipient leukemia cells compared with normal donor cells. Aim 2 focuses on patients who have relapsed despite allo-HCT and will test the efficacy and safety of a strategy that combines checkpoint blockade with adoptive cellular therapy manipulated to deplete regulatory T cells. Aim 3 will determine the safety and efficacy of combined IL-2 and ibrutinib therapy in patients with steroid-refractory chronic GVHD.

项目摘要疾病复发和移植与宿主疾病（GVHD）继续是改善预后的主要障碍对于患有同种异体造血细胞移植的血液系统恶性肿瘤的患者。项目1 将开发并实施一系列新型临床试验，以解决这些问题的三个特定目标。目标1 专注于基于免疫的策略，以防止接受HCT的髓样恶性肿瘤患者复发。其中包括临床研究以检查使用ipilumumab的检查点阻断的安全性和影响基于基因组的粒细胞恶性肿瘤患者，在同种HCT之后提早给药。在移植之前进行分析。我们还将完成一项预期的2阶段安慰剂控制的随机试验自体白血病细胞疫苗，用于分泌GM-CSF（GVAX）的基因工程针对患有活性疾病的Allo-HCT的髓样白血病患者进行预防。第三次审判将评估HCT设计后新型个人肽疫苗的影响，以靶向白血病。基于受体白血病细胞的基因组表征的新抗原和较小的组织相容性抗原与正常的供体细胞相比。 AIM 2专注于尽管Allo-HCT，但仍将测试的患者复发结合检查站封锁与收养蜂窝疗法的策略的功效和安全性操纵以耗尽调节性T细胞。 AIM 3将确定IL-2合并的安全性和功效类固醇难治性慢性GVHD患者的Ibrutinib治疗。