使用 CAR.CD30 重定向 T 淋巴细胞增强干细胞移植-猫眼课题宝

使用 CAR.CD30 重定向 T 淋巴细胞增强干细胞移植

批准号：

9104935

负责人：

Barbara Savoldo

金额：

$44.04万

依托单位：

UNIV OF NORTH CAROLINA CHAPEL HILL

依托单位国家：

美国

项目类别：

财政年份：

2013

资助国家：

美国

项目状态：

已结题

起止时间：

2013-09-01 至 2018-06-30

来源：

https://reporter.nih.gov/project-details/9104935

关键词：

Address Adjuvant Therapy Adoptive Transfer Aftercare Allografting Antibodies Antigen Receptors Antigen Targeting Antigens Autologous Autologous Stem Cell Transplantation Avidity Binding Biological Bulky Disease CD30 Antigens Cell Culture Techniques Cell Line Cells Clinical Cytotoxic T-Lymphocytes Development Disease Documentation Effector Cell Ensure Environment Generations Graft-Versus-Tumor Induction Health Hematologic Neoplasms Hodgkin Disease Immune Immune system Immunosuppression Immunosuppressive Agents Immunotherapy In Vitro Individual Infusion procedures Interleukin-15 Lymphoid Lymphoma Lytic Malignant Neoplasms Mediating Molecular Profiling Monitor Non-Hodgkin&apos s Lymphoma Pathway interactions Patients Phase I Clinical Trials Recruitment Activity Recurrence Refractory Refractory Disease Regulatory T-Lymphocyte Relapse Residual state Resistance Retroviridae Risk Safety Site Stem cell transplant Surface T cell therapy T-Cell Immunologic Specificity T-Cell Receptor T-Lymphocyte TNFRSF8 gene Testing Toxic effect Transplantation Treatment Failure Tumor Antigens Tumor Burden Tumor Lysis Syndrome arm base burden of illness clinical application cytokine cytotoxic density experience high risk in vivo man neoplastic cell novel outcome forecast phase 1 study prevent receptor reconstitution success tumor tumor microenvironment

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DESCRIPTION (provided by applicant): Stem cell transplantation is frequently used as a consolidation or salvage treatment for many patients with poor prognosis hematological malignancies. However, disease recurrence remains the major cause of treatment failure after autologous SCT, as the graft-versus-tumor (GVT) effects mediated by the donor-derived immune components infused with an allograft are lacking. Hence development of non-toxic "consolidation treatments" after transplant remains a highly desirable objective and the adoptive transfer of antigen/tumor-specific cytotoxic T lymphocytes (CTLs) is one promising approach. The introduction of chimeric antigen receptors (CARs) into T cells allows the rapid generation of effector cells specific for virtually any surface molecule and has significantly increased the clinical applicability of adoptive transfer of tumor-specific CTLs. Our central hypothesis is that y combining ASCT with tumor directed CAR+ T cells it should be possible to retain the superior safety of autologous SCT, whilst adding an effective GVT component. We propose to test this hypothesis in patients with CD30+ malignancies (including HL and ALCL) undergoing ASCT and at high risk of relapse, as we have a novel CAR targeting the CD30 molecule and new immune-based approaches are urged to prevent the diseases recurrence after ASCT in these patients. In the proposed phase I study we will address if combining CAR-based therapies with ASCT will reduce the risk of toxicities associated with high tumor burden, tumor immune evasion of this cell therapy, and if T cells grafted with our novel CAR and expended in IL-15 will have enhance persistence, expansion and in vivo activity. On completion of this first-in-man study we will know whether the infusion of CAR+ T cells is safe, and whether the cells persist and have in vivo functionality. All components to execute the study are in place and we have sufficient individual and institutional experience to ensure the study will be opened, completed and analyzed as planned, providing valuable information about the use of T cell immunotherapy after SCT.

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