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：
10465093
负责人：
Robert Jon Soiffer
金额：
$ 60.05万
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/10465093
关键词：
AML/MDS Address Adoptive Cell Transfers Adoptive Immunotherapy Allogenic Antigen-Antibody Complex Antigens Autologous B-Lymphocytes 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 Placebo Control 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

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.

项目概要疾病复发和移植物抗宿主病（GVHD）仍然是改善预后的主要障碍适用于接受同种异体造血细胞移植的血液恶性肿瘤患者。项目1 将开发和实施一系列新颖的临床试验来解决 3 个具体目标中的这些问题。目标1 专注于基于免疫的策略，以防止接受 HCT 的骨髓恶性肿瘤患者复发。其中包括检查伊匹鲁玛检查点阻断的安全性和影响的临床研究根据基因组结果，在具有高复发风险的骨髓恶性肿瘤患者的异基因 HCT 后早期进行治疗移植前进行分析。我们还将完成一项前瞻性 2 期安慰剂对照随机试验经基因工程改造可分泌 GM-CSF (GVAX) 的自体白血病细胞疫苗预防性地用于患有活动性疾病的进入同种异体 HCT 的髓系白血病患者。第三次审判将评估针对白血病特异性的 HCT 后新型个人肽疫苗的影响基于受体白血病细胞基因组特征的新抗原和次要组织相容性抗原与正常供体细胞相比。目标 2 重点关注接受异基因 HCT 后复发的患者，并将进行测试检查点阻断与过继性细胞疗法相结合的策略的有效性和安全性操纵以耗尽调节性 T 细胞。目标 3 将确定联合使用 IL-2 和依鲁替尼治疗类固醇难治性慢性 GVHD 患者。