5种程序性细胞死亡蛋白1抑制剂的Mini卫生技术评估

目的：通过对纳武利尤单抗、帕博利珠单抗、特瑞普利单抗、信迪利单抗、卡瑞利珠单抗这5种程序性细胞死亡蛋白1（programmed cell death protein 1，PD1）抑制剂进行Mini卫生技术评估，以期为药品遴选、药品安全合理使用提供依据。方法：本文从必要性、有效性、安全性、经济性、国家医保药物、国家基本药物、一致性评价、贮藏条件、有效期、全球使用情况和企业信誉度共11个方面对5种PD1抑制剂进行Mini卫生技术评估。结果：基于上述评估标准，5种PD1抑制剂的评分在58~75分之间。安全性上，PD1抑制剂的免疫相关性不良反应，尤其是心肌炎与神经系统症状在临床应用中应密切关注。结论：Mini卫生技术评估在多维度评估药品，能为医院药品遴选、安全合理使用提供依据，有一定的推广价值。     

Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice

JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (^nat/124/125I) to label JS001 probes to target the human PD1 (hPD1) antigen. In vitro, the half maximal effective concentration (EC₅₀) value of ^natI-JS001 did not significantly differ from that of JS001. The uptake of ¹²⁵I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of ¹²⁵I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized PD1 C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous ¹²⁴I-human IgG (¹²⁴I-hIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the ¹²⁴I-JS001 group at different time points was significantly higher than that of the blocking group or the ¹²⁴I-hIgG group in the humanized PD1 mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.     

Erythroderma caused by apatinib combined with toripalimabCSCD

A 66⁃year⁃old male patient with malignant melanoma received combined treatments with apatinib (oral 250 mg once daily), temozolomide (oral 500 mg on day 1 and 400 mg/d on days 2⁃4), toripalimab(240 mg intravenous infusion on days 1 and 15). After 5 cycles (28 days as a cycle), the patient developed multiple rashes, which were not alleviated after reducing the dose of apatinib to 250 mg orally once every 3 days in the 6th treatment cycle. Laboratory tests showed that serum albumin was 28.5 g/L, total serum protein was 55.5 g/L, eosinophil percentage was 0.096, and venous potassium was 3.17 mmol/L. Erythroderma caused by combination of apatinib and toripalimab was considered, and the 2 drugs were stopped. The patient received the treatments of methylprednisolone, loratadine, diphenhydramine, tria-mcinolone acetonide and econazole nitrate cream and mupirocin ointment (external coating), and skin care. At the same time, symptomatic treatments such as protein supplement, diuresis, potassium supplement, and stomach protection were given. After 10 days of treatments, the rash subsided, and desquamation and itching were improved. © 2023 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.