基于脂质纳米颗粒的多尺度系统性免疫编程用于癌症治疗
Lipid nanoparticle-based multi-scale systemic immune programming for cancer therapy.
目前,肿瘤免疫治疗的临床适用范围受到脱靶毒性、实体瘤中的物理屏障以及个性化细胞疗法复杂制造工艺的限制。
英文原题:Humoral response to mRNA-based COVID-19 vaccine and booster effect of a third dose in patients with mature T cell and NK-cell neoplasms.
在这项纳入 19 例成熟 T/NK 细胞肿瘤患者的研究中,于第二剂 mRNA 疫苗接种后 3 个月、6 个月和 9 个月检测了抗严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)刺突抗体。
淋巴系统恶性肿瘤患者受疾病本身及其治疗影响,体液免疫受损,因此发生重症2019冠状病毒病(COVID-19)和疫苗应答降低的风险较高。然而,成熟T细胞和NK细胞肿瘤患者对COVID-19疫苗的应答数据非常有限。本研究纳入19例成熟T/NK细胞肿瘤患者,在第二剂mRNA疫苗接种后3、6和9个月检测抗严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)刺突蛋白抗体。第二剂和第三剂疫苗接种时,分别有31.6%和15.4%的患者正在接受积极治疗。所有患者均完成基础疫苗接种,第三剂接种率为68.4%。与健康对照(HC)相比,成熟T/NK细胞肿瘤患者第二剂接种后的血清转化率(p<0.01)和抗体滴度(p<0.01)均显著较低。接受加强剂的患者,其抗体滴度仍显著低于HC(p<0.01);然而,患者血清转化率达到100%,与HC相同。加强接种可显著提高老年患者的抗体水平;这类患者接种两剂后的应答本来弱于较年轻患者。较高抗体滴度和较高血清转化率与感染率及死亡率降低相关,因此,对于成熟T/NK细胞肿瘤患者,尤其是老年患者,接种超过三剂可能有益。临床试验注册号:UMIN 000,045,267(2021年8月26日)和000,048,764(2022年8月26日)。
Patients with lymphoid malignancies have impaired humoral immunity caused by the disease itself and its treatment, placing them at risk for severe coronavirus disease-19 (COVID-19) and reduced response to vaccination. However, data for COVID-19 vaccine responses in patients with mature T cell and NK-cell neoplasms are very limited. In this study of 19 patients with mature T/NK-cell neoplasms, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike antibodies were measured at 3 months, 6 months, and 9 months after the second mRNA-based vaccination. At the time of the second and third vaccinations, 31.6% and 15.4% of the patients were receiving active treatment. All patients received the primary vaccine dose and the third vaccination rate was 68.4%. In patients with mature T/NK-cell neoplasms, both seroconversion rate (p < 0.01) and antibody titers (p < 0.01) after the second vaccination were significantly lower than those in healthy controls (HC). In individuals who received the booster dose, patients had significantly lower antibody titers than those in HC (p < 0.01); however, the seroconversion rate in patients was 100%, which was the same as that in HC. The booster vaccine resulted in a significant increase of antibodies in elderly patients who had shown a response that was inferior to that in younger patients after two doses of vaccination. Since higher antibody titers and higher seroconversion rate reduced the incidence of infection and mortality, vaccination more than three times may have the advantage for patients with mature T/NK-cell neoplasms, especially in elderly patients. Clinical trial registration number: UMIN 000,045,267 (August 26th, 2021), 000,048,764 (August 26th, 2022).
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