In recent years, chimeric antigen receptor (CAR) modified T cells have been used as a treatment for haematological malignancies in several phase I and II trials and with Kymriah of Novartis and Yescarta of KITE Pharma, the first CAR T cell therapy products have been approved. Promising clinical outcomes have yet been tempered by the fact that many therapies may be prohibitively expensive to manufacture. The process is not yet defined, far from being standardised and often requires extensive manual handling steps. For academia, big pharma and contract manufacturers it is difficult to obtain an overview over the process strategies and their respective advantages and disadvantages. This review details current production processes being used for CAR T cells with a particular focus on efficacy, reproducibility, manufacturing costs and release testing. By undertaking a systematic analysis of the manufacture of CAR T cells from reported clinical trial data to date, we have been able to quantify recent trends and track the uptake of new process technology. Delivering new processing options will be key to the success of the CAR-T cells ensuring that excessive manufacturing costs do not disrupt the delivery of exciting new therapies to the wide possible patient cohort.

BackgroundWorldwide, depression is rated as the fourth leading cause of disease burden and is projected to be the second leading cause of disability by 2020. Annual depression-related costs in the United States are estimated at US $210.5 billion, with employers bearing over 50% of these costs in productivity loss, absenteeism, and disability. Because most adults with depression never receive treatment, there is a need to develop effective interventions that can be more widely disseminated through new channels, such as employee assistance programs (EAPs), and directly to individuals who will not seek face-to-face care.ObjectiveThis study evaluated a self-guided intervention, using the MoodHacker mobile Web app to activate the use of cognitive behavioral therapy (CBT) skills in working adults with mild-to-moderate depression. It was hypothesized that MoodHacker users would experience reduced depression symptoms and negative cognitions, and increased behavioral activation, knowledge of depression, and functioning in the workplace.MethodsA parallel two-group randomized controlled trial was conducted with 300 employed adults exhibiting mild-to-moderate depression. Participants were recruited from August 2012 through April 2013 in partnership with an EAP and with outreach through a variety of additional non-EAP organizations. Participants were blocked on race/ethnicity and then randomly assigned within each block to receive, without clinical support, either the MoodHacker intervention (n=150) or alternative care consisting of links to vetted websites on depression (n=150). Participants in both groups completed online self-assessment surveys at baseline, 6 weeks after baseline, and 10 weeks after baseline. Surveys assessed (1) depression symptoms, (2) behavioral activation, (3) negative thoughts, (4) worksite outcomes, (5) depression knowledge, and (6) user satisfaction and usability. After randomization, all interactions with subjects were automated with the exception of safety-related follow-up calls to subjects reporting current suicidal ideation and/or severe depression symptoms.ResultsAt 6-week follow-up, significant effects were found on depression, behavioral activation, negative thoughts, knowledge, work productivity, work absence, and workplace distress. MoodHacker yielded significant effects on depression symptoms, work productivity, work absence, and workplace distress for those who reported access to an EAP, but no significant effects on these outcome measures for those without EAP access. Participants in the treatment arm used the MoodHacker app an average of 16.0 times (SD 13.3), totaling an average of 1.3 hours (SD 1.3) of use between pretest and 6-week follow-up. Significant effects on work absence in those with EAP access persisted at 10-week follow-up.ConclusionsThis randomized effectiveness trial found that the MoodHacker app produced significant effects on depression symptoms (partial eta2 = .021) among employed adults at 6-week follow-up when compared to subjects with access to relevant depression I...

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