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 specificity 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 emerging 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 on-target toxicity,notably due to cytokine release syndrome. Furthermore,efficacy in the context of solid tumours remains unproven,owing in part to lack of availability of safe tumour-specific targets,inadequate CAR T-cell homing and hostility of the tumour microenvironment to immune effector deployment. Manufacture and commercial development of this strategy also impose new challenges not 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 information to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general however, 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 efficient completion of necessary tests. Consequently, the need and appropriate minimum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeated performance of several common immunology investigations has been evaluated, based upon published evidence. In some cases(e.g., paraprotein quantification, or measurement of anti-glomerular basement membrane antibodies), repeated testing provides vital clinical information and can be justified on a frequent and individualized basis. However, many other investigations provided by immunology services provide lessvaluable information when used to aid disease monitoring 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 minimum 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.