CpG Plus Rituximab Therapy in Follicular Lymphoma

描述（由申请人提供）：尽管已经开发了治疗滤泡性淋巴瘤（FL）的新治疗方法，但总体生存率尚未得到显著改善。抗CD20单克隆抗体利妥昔单抗作为治疗FL的单一药物具有显著的但有限的活性。免疫刺激DNA寡核苷酸（ISS）具有多效性效应，包括增强抗原呈递和共刺激分子表达、刺激树突状细胞成熟、诱导细胞因子和增强抗体依赖性细胞介导的细胞毒性。通过对适应性和先天免疫的影响，我们假设ISS可能与利妥昔单抗协同作用。鉴于利妥昔单抗在ISS（1018）I期研究中具有良好的安全性和生物活性证据，我们计划在复发性FL患者的II期研究中评估利妥昔单抗与1018 ISS。我们提出三个目标。首先，进行1018 ISS与利妥昔单抗治疗复发性FL患者的临床试验。其次，研究1018 ISS与利妥昔单抗联合对效应细胞和肿瘤微环境的原位作用。第三，研究1018 ISS和利妥昔单抗对体外免疫应答的影响。这项研究是一种新的方法来治疗FL，其中增强抗原呈递和效应细胞可能会导致增强利妥昔单抗的细胞毒作用，并诱导抗肿瘤免疫。

DESCRIPTION (provided by applicant): Although novel therapeutic approaches have been developed for treating follicular lymphomas (FL), the overall survival has not yet been significantly improved. The anti-CD20 monoclonal antibody rituximab, has significant, albeit limited activity as a single agent for treatment of FL. Immunostimulatory DNA oligonucleotides (ISS) have pleotropic effects, including enhancement of antigen presentation and co-stimulatory molecule expression, stimulation of dendritic cell maturation, and induction of cytokines and augmented antibody-dependent cell-mediated cytotoxicity. Through effects on both adaptive and innate immunity, we hypothesize ISS may synergize with rituximab. Given a favorable safety profile, and evidence of biologic activity in a phase I study of ISS (1018) with rituximab, we plan to evaluate rituximab with 1018 ISS in a phase II study for relapsed FL patients. We propose three aims. First, to undertake a clinical trial of 1018 ISS with rituximab for patients with relapsed FL. Second, to investigate in situ effects of the combination 1018 ISS and rituximab on effector cells and the tumor microenvironment. Third, to investigate effects of 1018 ISS and rituximab on the immune response in vitro. This study is a novel approach to treating FL, where augmenting antigen presentation and effector cells may lead to enhanced cytotoxic effects of rituximab and induce anti-tumor immunity.