Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway; K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway;
K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology.
Blood. 2015 Jan 1;125(1):82-9. doi: 10.1182/blood-2014-07-592162. Epub 2014 Oct 7.
Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at www.clinicaltrials.gov as #NCT01926639.
晚期滤泡性淋巴瘤（FL）无法通过常规疗法治愈。在本项初步临床试验中，我们探索了一种新型局部免疫治疗策略的疗效和免疫原性。纳入了 14 名未经治疗或复发的 III/IV 期 FL 患者，对其进行孤立性淋巴瘤结节局部放射治疗，并在同一部位注射低剂量利妥昔单抗（5mg）、未成熟自体树突状细胞和粒细胞-巨噬细胞集落刺激因子，共 3 次，每次针对不同的淋巴瘤结节。主要终点为临床反应和全身性免疫诱导。14 名患者中有 5 名（36%）显示出客观的临床反应，包括 1 名皮肤 FL 患者，其皮肤病变消退。2 名患者获得持久的完全缓解。值得注意的是，接种诱导的全身性 CD8 T 细胞介导的反应与总肿瘤面积的减少密切相关（r=0.71，P=0.006），免疫应答者表现出延长的无治疗时间。临床应答者在治疗前的肿瘤负担并不低于无应答者，表明一旦诱导了免疫反应，T 细胞可以消除大的肿瘤块。总之，3 种治疗方法的联合应用，以及单个淋巴瘤结节的局部给药，介导了全身性 T 细胞免疫，并伴有播散性 FL 的消退。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT01926639。
