Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.

Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.

Reconciling predicted and measured viscosity parameters in high concentration therapeutic antibody solutions.

Monoclonal antibody (mAb) solution viscosity in ultra-high concentration formulations is a key developability consideration in mAb development risk mitigation strategies that has implications for downstream processing and patient safety. Predicting viscosity at therapeutically relevant concentrations remains critical, despite the need for large mAb quantities for viscosity measurement being prohibitive. Using a panel of IgG1s, we examined the suitability of viscosity prediction and fitting models at different mAb test concentration regimes.

Silicone as a smart solution for simulating soft tissue-an iterative approach to developing a high-fidelity sustainable training model for laparoscopic appendectomy.

Background: Laparoscopic appendectomy (LA) is an effective treatment for the surgical care of appendicitis, with this minimally invasive approach allowing patients to typically spend less time in hospital and promptly return to normal life activities. Residents can acquire the competence and confidence needed in a safe learning environment prior to real patient encounters through simulation-based learning of these techniques. We propose a low cost, sustainable, high fidelity simulation-based training model for LA to compliment regular resident practice of these skills.

Modulation of AAV transduction and integration targeting by topoisomerase poisons.

Adeno-associated virus (AAV) is a widely used vehicle for gene delivery, lending interest to developing methods for enhancing AAV transduction and transgene expression. Here, we profile the function of several topoisomerase poisons, which are small molecules that stabilize topoisomerase enzymatic intermediates, where topoisomerase enzymes are covalently bound at chromosomal DNA breaks. As previously observed, we found that the topoisomerase poisons camptothecin (CPT), doxorubicin (DOX), and etoposide (ETO) increased AAV transduction in cultured cell models.