Grille Sofía, Moreno María, Bascuas Thais, Marqués Juan M, Muñoz Natalia, Lens Daniela, Chabalgoity Jose A
Laboratory for Vaccine Research, Depto Desarrollo Biotecnológico, Facultad de Medicina, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay; Departamento Básico de Medicina, Facultad de Medicina, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
Immunology. 2014 Nov;143(3):428-37. doi: 10.1111/imm.12320.
Despite the efficacy of current immune-chemotherapy for treatment of B-cell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haemato-oncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8(+) T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials.
尽管目前的免疫化疗对治疗B细胞非霍奇金淋巴瘤有效,但仍有相当一部分患者复发,这凸显了对新治疗方式的需求。自科利毒素以来,利用活微生物开发抗肿瘤疗法不断发展,如今再次受到关注。鼠伤寒沙门氏菌在许多实体癌模型中已被证明是一种高效的抗肿瘤剂,但尚未用于血液肿瘤学。在此,我们报告肿瘤内注射LVR01(具有安全特性的减毒鼠伤寒沙门氏菌菌株)可引发局部和全身抗肿瘤免疫,从而延长淋巴瘤模型中的生存期。LVR01诱导肿瘤内中性粒细胞和活化的CD8(+) T细胞募集,同时提高自然杀伤细胞的活化状态。此外,还观察到具有明确1型辅助性T细胞特征的全身性特异性抗肿瘤反应。这种方法是淋巴瘤患者的一种替代治疗策略,可轻松进入临床试验。