van 't Land Freek R, Lau Sai P, de Koning Willem, Klaase Larissa, Vink Madelief, van Krimpen Anneloes, Dumas Jasper, Vadgama Disha, Nuyttens Joost J, Mustafa Dana A M, Stadhouders Ralph, Willemsen Marcella, Stubbs Andrew P, Aerts Joachim G, van Eijck Casper H J
Department of Surgery, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Department of Pathology and Clinical Bioinformatics, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Cancers (Basel). 2022 Oct 27;14(21):5299. doi: 10.3390/cancers14215299.
Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients.
LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood.
Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16-CD11b+HLA-DR myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3.
Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.
局部晚期胰腺癌（LAPC）患者接受化疗。在某些情况下，可在治疗方案中加入立体定向体部放疗（SBRT）。我们推测，在SBRT基础上加用含热灭活分枝杆菌的佐剂（IMM-101）可能会产生有益的免疫调节作用，从而提高生存率。本研究旨在探讨在SBRT中加入IMM-101的安全性，并研究联合治疗对LAPC患者外周血的免疫调节作用。
LAPC患者接受SBRT（40 Gy）和6次皮内注射1毫克IMM-101。主要终点是观察到的4级或更高等级的毒性发生率。对外周血进行靶向基因表达谱分析和多色流式细胞术以进行纵向免疫监测。
20例患者接受了研究治疗。未发生4级或更高等级的治疗相关不良事件。SBRT/IMM-101治疗导致不同淋巴细胞亚群短暂减少，CD14+CD16-CD11b+HLA-DR髓源性抑制细胞增加。重要的是，治疗显著增加了活化的ICOS+、HLA-DR+和Ki67+PD1+ T细胞和NK细胞频率。这并未伴随大多数抑制性标志物（如TIM-3和LAG-3）水平的升高。
SBRT与热灭活分枝杆菌疫苗联合治疗安全且具有免疫刺激作用。
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