For most therapeutic proteins, a long serum half-life is desired. Studies have shown that decreased antigen binding at acidic pH can increase serum half-life. In this study, we aimed to investigate whether pH-dependent binding sites can be introduced into antigen binding crystallizable fragments of immunoglobulin G1 (Fcab). The C-terminal structural loops of an Fcab were engineered for reduced ...

Tertiary lymphoid structures (TLS) are ectopic organs that arise in nonlymphoid tissue sites of chronic inflammation including tumours. The presence TLS, has been associated with increased tumour antigen presentation and improved cytokine-mediated signalling activity against cells. Due to this, TLS have favourable outcomes a number cancer types. There is limited data regarding the prevalence pr...

An optical biosensor for proteomic breast cancer biomarker detection in complex media is presented. Bloch Surface Waves (BSW) excited onto one dimensional photonic crystal (1DPC) were used to probe the interaction of HER2 with three antibody species and an inert protein (Bovine Serum Albumin - BSA). The system combines Label-Free readings track bioassay real-time development Fluorescence emissi...

Evolution of therapeutic monoclonal antibodies significantly benefited from the recombinant DNA technologies that are used to generate chimeric, humanized, and human versions of monoclonal antibody to reduce the problem of immunogenicity and neutralization, as well as from understanding mechanisms of action mediated by monoclonal antibodies (Nelson et al., 2010; Reichert, 2009; Ranson & Sliwkow...

Spacer or co-stimulatory components in chimeric antigen receptor (CAR) design influence CAR T cell effector function. Few preclinical mouse models optimally support candidate pre-selection for clinical development. Here we use a model which murine cells can be exploited with human tumor xenografts. This mouse-in-mouse approach avoids limitations caused by species-specific factors crucial surviv...

The actin cytoskeleton is an attractive target for bacterial toxins. The ADP-ribosyltransferase TccC3 from the insect bacterial pathogen Photorhabdus luminescence modifies actin to force its aggregation. We intended to transport the catalytic part of this toxin preferentially into cancer cells using a toxin transporter (Protective antigen, PA) which was redirected to Epidermal Growth Factor Rec...

Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brai...

Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. Objective: To employ rec...

Tumor-targeted antibody therapy has had a major impact on reducing morbidity and mortality in a wide range of cancers. Antibodies mediate their antitumor activity in part by activating immune effector cells; however, the tumor microenvironment (TME) is enriched with cellular and soluble mediators that actively suppress generation of antitumor immunity. Here, we investigate the potential of pros...