Frontier of therapeutic antibody discovery:The challenges and how to face them

Therapeutic monoclonal antibodies have become an important class of modern medicines.The established technologies for therapeutic antibody discovery such as humanization of mouse antibodies,phage display of human antibody libraries and transgenic animals harboring human IgG genes have been practiced successfully so far,and many incremental improvements are being made constantly.These methodologies are responsible for currently marketed therapeutic antibodies and for the biopharma industry pipeline which are concentrated on only a few dozen targets.A key challenge for wider application of biotherapeutic approaches is the paucity of truly validated targets for biotherapeutic intervention.The efforts to expand the target space include taking the pathway approach to study the disease correlation.Since many new targets are multi-spanning and multimeric membrane proteins there is a need to develop more effective methods to generate antibodies against these difficult targets.The pharmaceutical properties of therapeutic antibodies are an active area for study concentrating on biophysical characteristics such as thermal stability and aggregation propensity.The immunogenicity of biotherapeutics in humans is a very complex issue and there are no truly predictive animal models to rely on.The in silico and T-cell response approaches identify the potential for immunogenicity;however,one needs contingency plans for emergence of antiproduct antibody response for clinical trials.

Effect of paraoxonase1 gene polymorphism on carotid plaque and cerebral infarction in Hainan population

Objective:To investigate the effect of paraoxonase 1 gene polymorphism on carotid plaque stability with cerebral infarction in Hainan population.Methods:277 patients of caroticl plaque With cerebral infarction who underwent physical examination in a hospital in Hainan from 2015 to another awarding 2018 were selected as the experimental group and the 363 people who no cerebral infarction as the Analytical methods:control group.The clinical data analyzed.DNA was collected from peripheral blood of two groups of patients and genotyped by flight mass analytical methods.''AG and GG could be detected by rs3917538.The distribution frequencies of The three genotypes in The control group accorded with Hardy-Weinberg equilibrium.Results:The distribution frequencies of AA,AG and GG in the control group were 97(26.7%),175(48.2%)and 91(25.1%)respectively.In the experimental group,the distribution frequencies were 76(27.4%),136(49.1%)and 65(23.5%).There were no statistical differences among the three detection methods of co-dominant model,Dominant model and recessive model.There was no difference in the frequency of allele A and G between groups.Conclusion:Polymorphism of paraoxonase 1 gene rs3917538 has No significant effect on carotid plaque formation and cerebral infarction in Hainan population.The Supplementary sample size to add more SNP research sites for further study,It is expected to further Revral the relationship between PON1and carotial piaque complicatecl with cerebral infarction in Hainan.

Analysis of the hemodynamics changes of ipsilateral extracranial carotid artery with middle cerebral artery stenosis or occlusion patients

Objective: By observing the relation between middle cerebral artery stenosis or occlusion patients with ipsilateral extracranial carotid artery hemodynamics changes, to identify the value of hemodynamic change of extracranial carotid artery in predicting the middle cerebral artery stenosis, in order to improve the detection rate and accuracy. Methods: Eighty-three patients with unilateral severe middle cerebral artery stenosis or occlusion who confirmed by MRA were enrolled in the study, in all case were detected by TCD. The relationship of hemodynamic between extracranial carotid arteries and intracranial carotid arteries were analyzed. Results:The patients with severe middle cerebral artery stenosis or occlusion tend to have lower velocity and higher pulsitility index (PI). The PI(iCA), Vm(iCA) has a certain significance. The PI difference of carotid artery, end diastolic velocity of internal carotial artery (Vd (iCA) ) can evaluate stenosis of MCA more sensitive. The PI difference of common carotid artery=0.13, PI difference of internal carotid artery=0.15, Vd (iCA) =13.8 cm/s, Yonden index were 0.709, 0.710, 0.601.Sensitivity were 80.49%, 78.05%, 80.49%.Specificity were 90.48%, 92.86%, 78.57%;Positive predictive value were 89.20%, 91.42%, 78.57%.Negative predictive value were 82.60%, 81.25%, 80.48%. Conclusion: The patients tend to have lower velocity and higher PI. The PI difference of carotid artery, Vd(iCA), PI(iCA), Vm (iCA) severe middle cerebral artery stenosis or occlusion can be evaluated and provide a basis for the early diagnosis.