Acute hemorrhagic and necrotizing pancreatitis (AHNP) was induced by injection of sodium taurocholate into pancreatic and biliary duct of rats. TNFα MCAb was infused intravenously 15 minutes before pancreatitis was induced, and plasm TNFα level, serum lipase level and pancratic pathologic changes were tested.Results: the amount of ascites, serum lipase level and palsm TNFα level were significantly incresed and severe pancreatic pathologic changes was induced after AHNP, as compared with those in the control group .However, plasm TNFα level was not elevated after administration of TNFα MCAb, and the amount of ascites and pathologic damage to the pancreas were markely reduced. The animal fatality was reduced too. Conclusions: these suggest that TNFα play an important role in the pathogenesis of AHNP, and TNFα MCAb have a certain therapeutic effect on AHNP in rats.
Objective To study the effect of anti-CD40L monoclonal antibody on the rejection of rat pancreatic islet xenografts and its mechanism. Methods The animal models of human-rat pancreatic islet xenografts were established and were treated with anti-CD40L monoclonal antibody. The levels of blood glucose of transplantation rats were measured and the survival of grafts and transplantation rats were observed after transplantation. The morphological changes of grafts were observed and the levels of cytokines (IL-2 and TNF-α) were quantified by ELISA. Results ①Level of blood glucose in all the rats with diabetes decreased to normal on day (2.3±0.2) after transplantation. The average level blood glucose of control group began to increase on day (8.1±0.6), while the treatment group began to increase on day (18.5±1.2) after transplantation, which was significantly postponed compared with control respectively (P＜0.01). ②Grafts of treatment group and control group survived for (22±8.2) and (10±2.1) days respectively. Survival of grafts in treatment group was significant longer than that in control group (P＜0.01). ③Survival of transplantation rats were (35±6.5) and (21±5.7) days in treatment group and control group respectively. The survival of transplantation rats in treatment group was significant longer than that in control group (P＜0.05). ④Levels of serum IL-2 and TNF-α in control group increased dramatically within (3.2±0.3) days and reached peak within (7.3±0.5) days after transplantation, which were significantly higher than those measured before transplantation (P＜0.01); While in treatment group, the levels of serum IL-2 and TNF-α began to increase on day (22.6±1.7) after transplantation, and reached peak on day (28.5±2.2), which was significantly postponed than those in control group (P＜0.01). Conclusion Anti-CD40L monoclonal antibody can inhibit the rejection of rat pancreatic islet xenografts and prolong the survival time of transplantation rats and grafts.
The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.
ObjectiveTo investigate feasibility, safety, and problems to be solved in treatment with programmed death receptor protein-1 (PD-1) monoclonal antibody for patients with recurrent liver cancer after liver transplantation (LT).MethodAll of the domestic and foreign cases reports about the application of PD-1 monoclonal antibody in the patients with recurrent liver cancer after the LT were analyzed and summarized.ResultsIn six patients with recurrent liver cancer after the LT who received the PD-1 monoclonal antibody, the acute graft rejections were observed in 3 patients, 2 patients had the progressive disease but there was no evidence of the graft rejection, 1 patient achieved the complete response and there was no evidence of graft rejection and no side effects.ConclusionsAt present, effect of PD-1 monoclonal antibody therapy is still not sure in patients with recurrent liver cancer after LT. If PD-1 monoclonal antibody is used off-label, close surveillance is needed to discovery possible acute graft rejection.
ObjectiveTo investigate the influence of programmed cell death protein-1 (PD-1) monoclonal antibody on the anti-lung cancer effect of cytokine-induced killer cells (CIK) which were programmed in vitro. MethodsPeripheral blood mononuclear cells from 20 patients (8 males and 12 females with an average age of 56.45±5.89 years ranging from 42 to 65 years) diagnosed with advanced lung cancer from January to May 2019 at the Department of Oncology of Dalian Central Hospital were collected and induced to amplify into CIK cells in vitro. PD-1 monoclonal antibody combined with CIK cell culture group, individual cell culture group and PD-1 monoclonal antibody group were set up to detect the cell killing activity of CIK cells against lung cancer under different effective target ratio conditions, and the ratio of perforin and granzyme positive expression in PD-1 monoclonal antibody combined CIK cell culture group and individual CIK cell culture group was detected by flow cytometry. ELISA method was used to detect the interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) cytokine secretion levels in the two groups.ResultsThe killing effect of CIK cells on A549 lung cancer cells increased with the increase of effective target ratio by CCK8, and PD-1 monoclonal antibody increased the killing effect of CIK cells on A549 lung cancer cells under different effective target ratio, E∶T=5∶1 (28.5%±1.9% vs. 20.3%±1.8%), 10∶1 (40.6%±2.4% vs. 31.7%±2.1%), 20∶1 (57.4%±3.5% vs. 44.7%±3.8%), 40∶1 (74.1%±8.3% vs. 60.8%±5.3%). The killing effect of PD-1 monoclonal antibody combined with CIK cells and CIK cells alone on A549 lung cancer cells was statistically different (P<0.05). The killing effect of cells in both groups on lung cancer A549 cells was stronger than that of the PD-1 monoclonal antibody group (P<0.01). The results of flow cytometry showed that PD-1 monoclonal antibody increased the positive ratio of perforin and granzyme release in CIK cells, and the positive ratios of perforin release (46.7%±3.5%% vs. 35.1%±2.2%) and granzyme release (34.6%±3.8% vs. 25.7%±3.3%) in PD-1 monoclonal antibody combination with CIK cells group and CIK cells group were statistically different (P<0.05). Similarly, the secretion levels of IL-2, TNF-α, and IFN-γ cytokines were also increased in the PD-1 monoclonal antibody combined with CIK cells group compared with the CIK group (5 409.0±168.8 pg/mL vs. 4 300.0±132.3 pg/mL, 252.7±16.7 pg/mL vs. 172.5±8.6 pg/mL, 327.2±23.5 pg/mL vs. 209.7±16.0 pg/mL, P<0.05).ConclusionPD-1 monoclonal antibody can promote the release of tumoricidal substances in CIK cells and improve the killing effect of CIK cells on lung cancer A549 cells. It is speculated that the infusion of PD-1 monoclonal antibody before CIK cell adoption in lung cancer patients may be more beneficial to the treatment of disease. PD-1 monoclonal antibody combined with CIK cell therapy is promising as a new type of lung cancer immunotherapy.
Autoimmune hemolytic anemia (AIHA) is an autoimmune disease in which the life span of red blood cells is shortened by red blood cell autoantibodies. Due to immune intolerance and abnormal immune regulation, the hyperfunction of B lymphocytes produces too many red blood cell autoantibodies. Anti-CD20 monoclonal antibody is a second-line drug for warm antibody AIHA and first-line drug for cold antibody AIHA by reducing B lymphocytes. At present, the optimal dose of anti-CD20 monoclonal antibody in the treatment of AIHA has not been determined. There are no reports on the treatment of primary AIHA with second- or third-generation anti-CD20 monoclonal antibodies.
Anti-tumor necrosis factor-α monoclonal antibody agents have been widely applied in the management of autoimmune diseases. Among them, Adalimumab and Infliximab have been used for years in clinical practice in treating non-infectious uveitis and achieved satisfactory effects and safety. However, no guideline or expert consensus for their usage is available in China currently. It hopefully promotes standardized clinical application of anti-tumor necrosis factor -α monoclonal antibody in treating non-infectious uveitis, together with other senior experts in uveitis, the Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association form this evidence-based recommendations for clinicians’ reference.
As a new treatment option after conventional corticosteroids and immunomodulatory drugs, biologics have been widely used in the clinical management of non-infectious uveitis in many countries due to their approved efficacy and safety. Anti-tumor necrosis factor-alpha monoclonal antibody is the most commonly used one. However, the guidance on its standardized application is lacking. The Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association compiled the Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody. This evidence-based consensus is made according to the principle of consensus building and combines the clinical experience of the experts. Twelve recommendations are formatted on the application of Adalimumab and Infliximab. The interpretation of this consensus point will help improve the normative and effective application of anti-tumor necrosis factor-alpha monoclonal antibody in ophthalmologists, rheumatologists and immunologists.
ObjectiveTo investigate the effects of lenvatinib combined with transarterial chemoembolization (TACE) and programmed death protein-1 (PD-1) monoclonal antibody (Abbreviated as LEN-TAP regimen) on residual liver volume and surgical safety in intermediate and advanced hepatocellular carcinoma (HCC). MethodsThe clinicopathologic data of patients with intermediate and advanced HCC were collected retrospectively, who underwent the LEN-TAP conversion therapy and surgical resection in the Department of Liver Surgery, West China Hospital, Sichuan University from October 2020 to December 2021. The total liver volume, tumor volume, and residual liver volume of the patients before and after conversion therapy were analyzed. ResultsA total of 48 patients were included, 26 of whom had partial remission and 22 had stable disease, the objective response rate was 54.2% (26/48) according to the Response Evaluation Criteria in Solid Tumours 1.1 after conversion therapy. Before and after conversion therapy, the total liver volumes including tumor were (1 607.15±712.22) mL and (1 558.03±573.89) mL [mean difference (MD) and 95% confidence interval (CI)=–57.42(–134.30, 19.46), t=–1.503, P=0.140], the total liver volumes excluding tumor tissue were (1 095.28±227.60) mL and (1 260.31±270.71) mL [MD(95%CI)=165.03(128.13, 201.93), t=8.997, P<0.001], the tumor volumes were 260.25(107.75, 699.50) mL and 121.73 (33.00, 332.88) mL [MD(95%CI)=–222.45(–296.46, –148.44), Z=–5.641, P<0.001], and the residual liver volumes were (493.62±154.51) mL and (567.83±172.23) mL [MD(95%CI)=74.21(54.64, 93.79), t=7.627, P<0.001], respectively. The increase rates of tumor volume and residual liver volume after conversion therapy were (–53.34±33.05)% and (16.34±15.16)%, respectively. The conversional resections were successfully completed in all patients, with 13 (27.1%) cases experiencing postoperative complications and without occurrence of postoperative liver failure. ConclusionThe data analysis results of this study indicate that the LEN-TAP conversion therapy can shrink tumor volume and increase the residual liver volume for patients with intermediate and advanced HCC, which helps to improve the safety of conversion resection.