1.Improved immune response and anti-tumor effect of WT1 peptide emulsion adjuvant vaccine for acute myeloid leukemia
Yan YE ; Zelong ZHANG ; Baohang ZHU ; Shulin LIU ; Zhen SONG ; Qingpeng YUAN ; Yun YANG ; Haibo LI ; Quanmin ZOU ; Hao ZENG ; Hongwu SUN
Journal of Army Medical University 2024;46(9):1024-1033
Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P<0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P<0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P<0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P<0.05)and the proportion of specific CD8+T cells(P<0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5%,while all mice in the other groups had died(P<0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.
2. Causes analysis and evaluation of correlative factors of high perioperative blood transfusion demand for patients with lung tumors
Qingpeng ZENG ; Jiagen LI ; Fang LYU ; Jinfeng HUANG ; Liangze ZHANG ; Shugeng GAO ; Jun ZHAO
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(10):603-607
Objective:
To analyze the causes and correlative factors of high perioperative blood transfusion demand in patients with lung tumor, and to discuss the influence of high blood transfusion demand on patients’ postoperative recovery and its predictive factors.
Methods:
From November 2007 to October 2017, clinical data of patients who had underwent surgery for lung tumors in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences were collected. A total of 83 cases with perioperative transfusion of red blood cells ≥5U were classified as high transfusion demand group. Another 83 cases were selected from the rest of the patients with transfusion of red blood cells <5U as normal transfusion demand group. Related clinical and transfusion data were summarized to analyze the causes of high blood transfusion demand and its effect on postoperative recovery, univariate and multivariate logistic regressions were used to analyse correlative factors.
Results:
From November 2007 to October 2017, 23 898 patients with lung tumor underwent surgery in our department and the high blood transfusion demand rate was 0.35%. In the last 10 years, the ratio of high transfusion demand was 0.61%(46/7 503) in the first 5 years versus 0.23%(37/16 395) in the later 5 years(