NK CELL ACTIVATING RECEPTORS ON EFFECTOR CELLS IN MYELOMA PATIENTS RECEIVING TRA

接受 TRA 的骨髓瘤患者效应细胞上的 NK 细胞激活受体

• 批准号: 8168323
• 负责人: KENNETH Robert MEEHAN
• 金额: $ 23.98万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168323
• 关键词: Accounting; Blood; Cell Transplants; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; Data; Effector Cell; Funding; Grant; Growth Factor; Hematopoietic; Immune; Immunologics; Immunotherapy; Infusion procedures; Institution; Interleukin-2; Ligands; Mediating; Multiple Myeloma; Mus; Natural Killer Cells; Patients; Recovery; Regimen; Research; Research Personnel; Resources; Source; T-Lymphocyte; Transplantation; United States National Institutes of Health; cell killing; improved; in vivo; killings; neoplastic cell; receptor; reconstitution

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autolgous transplantation for myeloma improves survival, but the immunologic mechanisms accounting for this improvement are unknown. Our data indicate that NKG2D+CD8+T cells may be one reason for this benefit. NKG2D, one of four NK activating receptors, has been identified on some CD8+T cells that mediate TCR-independent and non-MHC restricted tumor cell killing. Since the NKG2D receptor recognizes ligands expressed on myeloma cells, these NKG2D+CD8+T cells aggressively kill myeloma cells and provide a unique immunotherapy opportunity. Immune mobilization, using IL-2 and growth factors (i.e. stimulation of hematopoietic cells into the blood that can be used for transplant) expands CD8+T cytotoxic cells that acquire the NKG2D receptor and perform their killing using NKG2D. We have identified an increase number and function of NKG2D+CD8+T cells in vivo early post-transplant. When murine CD8+T cells are transduced with a chimeric NKG2D receptor and injected into myeloma-bearing mice, 100% of the mice survive. We hypothesize that the infusion of immune mobilized cells into myeloma patients as part of the transplanted cells will markedly enhance immune reconstitution, by increasing the number and function of NKG2D+CD8+T cells. These proposed studies will define the presence, function and mechanisms of NK cell activating receptors on recovering CD8+T cells in vivo following transplant. Our long-term hypothesis is that this regimen will improve survival by enhancing early immune recovery following transplantation.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 骨髓瘤自体移植可提高生存率，但其免疫机制尚不清楚。我们的数据表明，NKG 2D + CD 8 +T细胞可能是这种获益的原因之一。NKG 2D是四种NK活化受体之一，已在一些CD 8 +T细胞上鉴定出，其介导TCR非依赖性和非MHC限制性肿瘤细胞杀伤。由于NKG 2D受体识别骨髓瘤细胞上表达的配体，因此这些NKG 2D + CD 8 +T细胞积极杀伤骨髓瘤细胞，并提供独特的免疫治疗机会。使用IL-2和生长因子（即刺激造血细胞进入可用于移植的血液）进行免疫动员，扩增获得NKG 2D受体的CD 8 +T细胞毒性细胞，并使用NKG 2D进行杀伤。我们已经确定了移植后早期体内NKG 2D + CD 8 +T细胞的数量和功能增加。当用嵌合NKG 2D受体转导鼠CD 8 +T细胞并注射到携带骨髓瘤的小鼠中时，100%的小鼠存活。我们假设，将免疫动员细胞作为移植细胞的一部分输注到骨髓瘤患者体内，将通过增加NKG 2D + CD 8 +T细胞的数量和功能，显著增强免疫重建。这些拟议的研究将确定NK细胞活化受体在移植后体内恢复CD 8 +T细胞的存在、功能和机制。我们的长期假设是，这种方案将通过增强移植后的早期免疫恢复来提高生存率。