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While pointing out shortcomings of the CCD blocker in this study, we should not ignore problems associated with the standard sIgE determinations applied here.
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Unfortunately, we could not evaluate the SI score as a predictive biomarker for checkpoint blockers in this study, because our patients did not receive this type of treatment.
The organization employing TD and FA holds IP rights on the CCD blocker described in this study.
The CRAC channel blockers used in this study were obtained from GlaxoSmithKline, UK.
Hence, the GSK blockers characterized in this study interfere with the permeation through the Orai pore by slow access to a site which is affected by alterations in the selectivity filter.
Although a different type of β blocker was used in this study, the findings are similar to data published by Haugaa et al who reported no effect of β-blocker therapy in 43% of subjects and that less severe arrhythmias were not decreased despite the maximum tolerated dose of β blocker.
Also, TNF-α expression may be different with a non-specific beta-blocker as used in this study when compared with studies utilizing beta-1 specific blockade.
However, Hogarth questions whether it makes sense to enroll patients who are already taking TNF-α blockers in the study, because it's difficult to distinguish between the effects of the gene-therapy product and the drugs.
However, the use of heroic doses of β-blockers in the study of Pasquier et al (2013) is of great concern.
The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/13/41/prepub We are grateful to Novartis and Boehringer Ingelheim for providing the IGF-IR tyrosine kinase inhibitor NVP-AEW541 and the pan-erbB blocker afatinib for use in this study.
In accordance with our daily clinical practice in KT recipients, all the patients received RAS blockers (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) prior to inclusion in this study.
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