Immune checkpoint is one of the most effective research targets for tumor immunotherapy. Immune checkpoint inhibitors, mainly programmed death receptor 1 and its ligand 1, have achieved good response rates in various tumor treatments, but some tumors still have low response rates. In recent years, bispecific antibodies have developed rapidly in the field of tumor research, because they can target multiple targets and play a combined role in tumor therapy, and can effectively inhibit tumor immune escape. This article reviews the research progress and clinical status of bispecific antibodies targeting immune checkpoints.

The clinical data,endoscopic and CT findings of 39 patients with Crohn's disease(CD) and 24 patients with intestinal tuberculosis (ITB) were retrospectively reviewed.Diarrhea,hematochezia,perianal disease,intestinal obstruction,occurred more frequently in CD than in ITB (P ＜0.05 or ＜0.01).Night sweating,febrility,pulmonary tuberculosis and ascites were more common in ITB than in CD (P ＜0.01).The endoscopic findings showed that longitudinal ulcer,cobblestone sign,intestinal stricture were detected more often in CD than in ITB (P ＜ 0.05 or ＜ 0.01),but transverse ulcer and rodent ulcer were more frequently found in ITB than in CD (P ＜0.05 or ＜0.01).On the CT imaging mural gas,fat,enteric cavity stenosis and layering thickening were more common in CD than in ITB (P ＜ 0.05 or ＜ 0.01),but mural single layer thickening and hollow lymph nodes were discovered more frequently in ITB than in CD (P ＜ 0.01).The degree of intestinal wall thickening,enhancement and lymph nodes enlargement of ITB were more severe than that of CD (P ＜ 0.01).The clinical manifestations combined with endoscopic and CT finding may improve the differential diagnosis between Crohn's disease and intestinal tuberculosis.

Objective To develop an ultrasmall superparamagnetic iron oxide(USPIO)based MR probe targeting CD40 mutant and investigate its biological and chemical properties and its targeting effect on ovarian cancer cells in vitro.Methods To prepare immunologically competent probe,the monoclonal antibody was conjugated with USPIO particles modified by DMSA based on chemical crosslinking method.The USPIO labeled anti-human CD40 mutant monoclonal antibody 5H6(5H6-USPIO)was the experimental probe,and the USPIO labeled anti-human CD40 monoclonal antibody 5C11(5C11-USPIO)and USPIO served as control agents.The flow cytometry,confocal microscopy and Prussian blue staining were employed to assess the magnetic performance and analyze its bioactivity of the probe.The probe's cell MR imaging in vitro was carried out using ovarian caner cells(HO8910)with high CD40 mutant expression.The analysis of signal data of different groups was conducted by using one-way ANOVA andLSD test.The probe's effect on ovarian caner cells' growth was measured by CCK-8 kit.Results The stable molecular probe carrying nanoparticles and CD40 mutant antibody was built and purified successfully.The probe had similar magnetic property compared with original USPIO.Immunofluorescence and Prussian blue staining confirmed that the molecular probe could recognize CD40 mutant on ovarian cancer cells(HO8910)with high specificity.The probe had no effect on the growth of HO8910 cells.MR cell imaging in vitro showed that the value of T2 and T2 * decreased significantly after the probe binding with HO8910 cells and T2WI became darker than control groups.The T2 and T2* relaxation time of 5H6-USPIO group was(40.05 ± 1.62)ms and(3.08 ± 0.11)ms,respectively.The T2 and T2 * relaxation time of 5H6-USPIO group was shorter than 5C11-USPIO [(85.38 ± 4.74)and(11.82 ± 1.00)ms,respectively]and USPIO[(91.62 ± 3.35)and(13.60 ± 1.92)ms,respectively]groups with statistical significance(F =196.29,60.73,P ＜0.01).The difference of T2 and T2* relaxation time between 5C11-USPIO and USPIO groups showed no statistical significance (P ＞0.05).Conclusions CD40 mutant antibody can conjugate with ultrasmall superparamagnetic iron oxide particles to form MR molecular probe using chemical crosslinking method.The probe has good magnetic characters and high bioactivity.The probe can specifically bind with HO8910 cells.

Objective To explore the value of single source dual energy CT for quantitative measurement of liver fat fraction in the rabbit model of nonalcoholic fatty liver disease(NAFLD).Methods Thirty male New Zealand rabbits were randomly divided into five groups.Six rabbits were fed with standard chow as a control group for 3 weeks.TwentyGfour rabbits were divided into four groups and fed with highGfat, highGcholesterol diet to reach different stage of NAFLD model for 1 ,3 ,4 and 8 weeks respectively before dualGenergy CT scanning.1 40 keV polychromatic CT values (QC),70 keV monochromatic CT values (Mono 70 keV),slope,effective atomic number (EffectiveGZ)and fat concentration based on dualGenergy CT fat decomposition (Fat/Water)were measured.Liver samples were obtained to measure the fat fraction and staged according to Burnt staging system.Correlations between different CT indexes and fat fraction were analyzed.ROC was used to evaluate the diagnosis efficacy of different parameters.Results Correlation between fat concentration based on dualGenergy CT fat decomposition and fat fraction (r＝0.936)was better than that between 140 keV polychromatic CT values (r＝－0.838)and 70 keV monochromatic CT values (r＝－0.906),as well as effective atomic number (r＝－0.858)and slope (r＝0.863).In terms of diagnostic performance of material decomposition fat imaging,the values of area under the curve were 0.944 (stage 0 vs.stage 1 or more severe),0.995 (stage 1 or less severe vs.stage 2 or more severe)and 1 (stage 2 or less severe vs.stage 3)with optimal cutoff values of 59.310,99.5 17 and 22 3.02 3 mg/cm3 ,respectively.Conclusion The dualGenergy CT can quantitatively measure liver fat concentration as a noninvasive surrogate bioGmarker in the rabbit model of nonalcoholic fatty liver disease.DualGenergy CT derived material decomposition fat images can provide more diagnostic information at the early stage of NAFLD.

Bispecific antibodies can target two different targets simultaneously with a wide application prospect and rapid development in tumor treatment. The main function is to recruit effector cells selectively in order to kill tumor cells or bind tumor-associated growth factor receptor to inhibit cell proliferation. This paper reviews the current situation of bispecific antibodies in design, mechanism of action and the research progress in the clinical cancer treatment.

Antibodies, Monoclonal ; chemistry ; immunology ; Antigens, Viral ; chemistry ; genetics ; immunology ; Binding Sites ; Capsid Proteins ; chemistry ; genetics ; immunology ; Epitopes ; chemistry ; genetics ; immunology ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Hepatitis E ; immunology ; prevention & control ; virology ; Hepatitis E virus ; chemistry ; immunology ; Humans ; Molecular Docking Simulation ; Mutagenesis, Site-Directed ; Peptide Mapping ; Protein Binding ; Recombinant Proteins ; chemistry ; genetics ; immunology ; Viral Hepatitis Vaccines ; administration & dosage ; biosynthesis

Monoclonal antibodies have become the main type of antibody drug because of their high specificity and strong affinity to antigen. However, with the intensive study of the natural monoclonal antibody, many defects have faced, such as the limit times of binding to antigen, the unanticipated antibody clearance and antigen accumulation. Therefore, studies are no longer limited to the natural antibody screening, but rather to improve the efficiency of antibody drugs by engineering. In recent years, the bottlenecks in the development of conventional antibody have been solved effectively since the discovery of a novel recycling antibody. Recycling antibody binds to an antigen in plasma and dissociates from the antigen in endosome, thus maximizing the use of antibody and reducing antigen-mediated antibody clearance and antibody-mediated antigen accumulation. In addition, recycling antibodies can enhance the affinity with Fc receptors through further Fc modification. This paper reviews the research progress of circulating antibodies, including its characteristics, transformation methods and prospects.
Antibodies, Monoclonal ; immunology ; Antigens ; Endosomes ; Protein Binding ; Receptors, Fc

Objective:To explore benefit finding and its influencing factors among enterostomy patients.Methods:A total of 120 enterostomy patients were investigated with general information questionnaire, Benefit Finding Scale, Simplified Scale of Resilience and Perceived Social Support Scale.Results:The score of benefit finding among enterostomy patients was 49.44±5.86. Multiple regression analysis showed that education level, self-care, complications, resilience, perceived social support were influencing factors of benefit finding, and explained 51.1% of the variance.Conclusions:The benefit finding among enterostomy patients was grim. It is suggested that clinical staff pay more attention to the patients with low education, poor self-care and complications of stoma, and also pay more attention to the positive psychology and the social support system of patients, guide patients to pay attention to the positive significance of the disease, so as to improve the level of benefit finding.

Objective:To investigate the current situation with regard to a sense of coherence in major caregivers of enterostomy patients and analyze its relationship with self-efficacy and perceived social support.Methods:From July to December 2019, a total of 118 major caregivers of enterostomy patients were investigated using a general information questionnaire, a self-efficacy scale, and a perceived social support scale.Results:The score of sense of coherence in major caregivers of enterostomy patients was 58.40±9.17, and the average scores of all dimensions, from high to low, were “controllable sense，” “understandable sense，”and “meaningful sense.” Sense of coherence was positively correlated with self-efficacy and perceived social support ( r=0.457, P<0.01; r=0.369, P<0.01). Hierarchical multiple regression analysis showed that self-efficacy and perceived social support had a positive predictive effect on sense of coherence and explained 35.2% of the variance ( R′ 2=0.352, F=25.639, P<0.001). Conclusions:The main caregivers of enterostomy patients had a low level of sense of coherence. Self-efficacy and perceived social support have a positive effect on sense of coherence. Medical staff should take targeted measures to help caregivers improve their self-efficacy and social support system in order to improve their sense of coherence.

Interleukin-12 (IL-12) is a pro-inflammatory cytokine derived from antigen-presenting cells. IL-12 has a variety of effector mechanisms such as promoting T cells proliferation and cytotoxicity, inducing T cells and NK cells to secrete interferon-γ (IFN-γ), etc. IL-12 shows significant anti-tumor effect in preclinical stage and is quickly used in clinic, but its systemic administration has serious dose-limiting toxicity. At present, most of the research is about the topical use of IL-12 to reduce systemic toxicity, change tumor microenvironment and activate immune system. This article reviews the research progress and clinical trials of IL-12 in the treatment of solid tumors in recent years.