TREATMENT OF CHRONIC LYMPHOCYTIC B-LEUKEMIA (B-CLL) WITH HUMAN IL-2 AND CD40

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 一、假说 CD40配体(CD40L)在体内增强白血病抗原提呈、作为共刺激分子和诱导hIL-2释放的能力都有助于招募特异性T细胞和NK细胞抗白血病效应机制，从而使hIL-2能够被进一步放大。 二、具体目标 -确定3~6次皮下注射来自慢性淋巴细胞白血病(B-CLL)患者的自体恶性B细胞的安全性，这些B-CLL患者的自体恶性B细胞已在体外被修饰为分泌人白细胞介素2(hIL-2)和表达人CD40配体(HCD40L)。 -确定SC注射经体外修饰的分泌hIL-2和表达hCD40L的B-CLL细胞是否诱导MHC限制性或非限制性抗肿瘤免疫反应。 -获得关于这一治疗方案的抗东帝汶效果的初步数据。

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. ABSTRACT I. HYPOTHESIS It is proposed that the ability of CD40 Ligand (CD40L) to enhance leukemia antigen presentation in vivo, to act as a co-stimulator molecule and to induce hIL-2 release all serve to recruit both specific T cell and NK cell anti-leukemia effector mechanisms, which hIL-2 is then able to further amplify. II. SPECIFIC AIMS - To determine the safety of three to six subcutaneous (SC) injections of autologous malignant B cells from chronic lymphocytic leukemia (B-CLL) patients, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L). - To determine whether MHC-restricted or unrestricted anti-tumor immune responses are induced by SC injections of B-CLL cells which have been modified ex vivo to secrete hIL-2 and to express hCD40L. - To obtain preliminary data on the anti-timor effects of this treatment regimen.