Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

No variance for filed orders: Hayes v Westpac Banking Corporation [2015] QCA 260

In Hayes v Westpac Banking Corporation [2015] QCA 260 the Queensland Court of Appeal examined the relationship between rules 7 (extending and shortening time) and 667 (setting aside) of the Uniform Civil Procedure Rules 1999 (Qld), and held that r667(1) does not enable the court to set aside or vary an order after the order has been filed. The court found that, to the extent that this conclusion was contrary to the decision in McIntosh v Linke Nominees Pty Ltd [2010] 1 Qd R 152, the decision in McIntosh was wrong and should not be followed.

A brilliant breakthrough in OI type V

Interferon-induced transmembrane protein 5 or bone-restricted i ifitm-like gene (Bril) was first identified as a bone gene in 2008, although no in vivo role was identified at that time. A role in human bone has now been demonstrated with a number of recent studies identifying a single point mutation in Bril as the causative mutation in osteogenesis imperfecta type V (OI type V). Such a discovery suggests a key role for Bril in skeletal regulation, and the completely novel nature of the gene raises the possibility of a new regulatory pathway in bone. Furthermore, the phenotype of OI type V has unique and quite divergent features compared with other forms of OI involving defects in collagen biology. Currently it appears that the underlying genetic defect in OI type V may be unrelated to collagen regulation, which also raises interesting questions about the classification of this form of OI. This review will discuss current knowledge of OI type V, the function of Bril, and the implications of this recent discovery.

Accountability for good faith in commercial dealing: The Carter v Boehm legacy 250 years on

In common law jurisdictions such as England, Australia, Canada and New Zealand good faith in contracting has long been recognised in specific areas of the law such as insurance law and franchising, and more recently the implied duties of good faith and mutual trust and convenience in employment contracts have generated a considerable volume of case law. Outside of these areas of law that may be characterised as being strongly‘relational’ in character,the courts in common law jurisdictions have been reluctant to embrace a more universal application of good faith in contracting and performance. However increasingly there are cases which support the proposition that there is a common law duty of good faith of general application to all commercial contracts. Most important in this context is the recent decision of the Supreme Court of Canada in Bhasin v Hrynew.1 However, this matter is by no means resolved in all common law jurisdictions. This article looks at the recent case law and literature and at various legislative incursions including statutes, codes of conduct and regulations impacting good faith in commercial dealings.