Chimeric antigen receptors:On the road to realising their full potential

Chimeric antigen receptors （CARs） are fusion molecules that may be genetically delivered ex-vivo to T-cells and other immune cell populations, thereby conferring specifcity for native target antigens found on the surface of tumour and other target cell types. Antigen recognition by CARs is neither restricted by nor dependent upon human leukocyte antigen antigen expression, favouring widespread use of this technology across transplantation barriers. Signalling is delivered by a designer endodomain that provides a tailored and target-dependent activation signal to polyclonal circulating T-cells. Recent clinical data emphasise the enormous promise of this emer-ging immunotherapeutic strategy for B-cell malignancy, notably acute lymphoblastic leukaemia. In that context, CARs are generally targeted against the ubiquitous B-cell antigen, CD19. However, CAR T-cell immunotherapy is limited by potential for severe ontarget toxicity, notably due to cytokine release syndrome. Furthermore, effcacy in the context of solid tumours remains unproven, owing in part to lack of availability of safe tumourspecific targets, inadequate CAR T-cell homing and hostility of the tumour microenvironment to immune effector deployment. Manufacture and commercial development encountered with more traditional drug products. Finally, there is increasing interest in the application of this technology to the treatment of non-malignant disease states, such as autoimmunity, chronic infection and in the suppression of allograft rejection. Here, we consider the background and direction of travel of this emerging and highly promising treatment for malignant and other disease types.

Role of the clinical immunology laboratory in disease monitoring

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

Modified Liujunzi Decoction (六君子汤) Alleviates Chemotherapy-Induced Anorexia in Advanced Non-Small Cell Lung Cancer: A Propensity Score Matched Case-Control Study

Objective:To evaluate the effect of Chinese herbal medicine formula,modified Liujunzi Decoction(六君子汤,MLJZT),for anorexia,utilized as adjunct therapy during chemotherapy treatment for patients with advaneed non-small cell lung cancer(NSCLC).Methods:The study adopted a propensity score-matched design based on a prospective database.From February 2016 to September 2017,patients with advanced NSCLC that received both cisplatin-based chemotherapy and MLJZT(IM group)were 1:1 propensity score-matched to patients that received the cisplatin-based chemotherapy alone(control group).Changes in anorexia and weight,as well as side effects were evaluated per week within 4-cycle chemotherapy.Results:Overall,156 patients with advaneed NSCLC that had received chemotherapy from our database were ide ntified and 53 pairs were matched successfully.In total,48.6%(50/53)of patients in the IM group had anorexia-improvement compared to 28.3%(15/53)of patients in the control group,and a total of 39.6%(21/53)of patients in the control group had a worsening of anorexia compared to only 7.8%(8/53)of patients in the IM group(P<0.01).The weight reduced significantly over time in the control group(-2.36±2.53 kg)as compared to the IM group(-0.62±3.89 kg,P<0.01).CHM didn't reduce the efficacy of chemotherapy in shrinking tumor size,and didn't increase the incidence of side effects such as hematological and hepatorenal toxicity.Conclusion:MLJZT is effective and safe for alleviating anorexia in patients with NSCLC.These fin dings warrant the con duct of a randomized con trolled trial.