Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.

Background: OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.

Methods: Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade.

Unlabelled: In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses.

Conformal orbit sparing radiation therapy: a treatment option for advanced skin cancer of the parotid and ear region.

Introduction: New surgical methods have enabled resection of previously in-operable tumours in the region of the parotid gland and ear. This has translated to deeper target volumes being treated with adjuvant radiotherapy. Due to the limitations of existing conformal techniques, alternative planning approaches are required to cover the target volume with appropriate sparing of adjacent critical structures.

Discovery of the first potent, selective 5-hydroxytryptamine1D receptor antagonist.

A series of 5-(piperidinylethyloxy)quinoline 5-hydroxytryptamine(1D) (5-HT(1D)) receptor antagonists have been discovered from elaboration of the series of dual 5-hydroxytryptamine(1)-selective serotonin reuptake inhibitors (5HT(1)-SSRIs) reported previously. This is the first report of highly potent, selective antagonists for the 5-HT(1D) receptor, which represents an extremely useful set of pharmacological tools for further understanding the roles of the 5-HT(1) receptor subtypes.

Assessment of pelvic stabilization devices for improved field reproducibility.

The aim of this study was to evaluate the improvement in patient comfort and field positional accuracy provided by a new pelvic stabilization system when delivering multiple field radiotherapy to the pelvis. The Pelvic Cradle (BEHTS Manufacturing, Brisbane, Qld, Australia) is a stabilization device that provides reproducible patient positioning and levelling. Ninety patients were randomized into three groups.