Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186.

Background: Despite clinical success with T cell engagers (TCEs) targeting hematological malignancies, achieving a safe and efficacious dose in patients with solid tumors remains challenging. Due to potency, low levels of target antigen expression on normal tissues may not be tolerated. To overcome this, we engineered a novel conditionally active TCE design called COBRA (nditional ispecific edirected ctivation).

Structural arrangement of the VH and VL domains in the COBRA™ T-cell engaging single-chain diabody.

Background: COBRA™ (COnditional Bispecific Redirected Activation) T-cell engagers are designed to target solid tumors as a single polypeptide chain prodrug that becomes activated by proteolysis in the tumor microenvironment. One COBRA molecule comprises seven Ig domains: three single-domain antibodies (sdAbs) recognizing a tumor target or human serum albumin (HSA), and CD3ε-binding variable fragment heavy chain (VH) and variable fragment light chain (VL) and their inactivated counterparts, VHi and VLi. Pairing of VH and VL, and VLi and VHi into single-chain variable fragments (Fv) is prevented by shortened inter-domain linkers.

COBRA™: a highly potent conditionally active T cell engager engineered for the treatment of solid tumors.

Conditionally active COBRA™ (COnditional Bispecific Redirected Activation) T cell engagers are engineered to overcome the limitations of inherently active first-generation T cell engagers, which are unable to discern between tumor and healthy tissues. Designed to be administered as prodrugs, COBRAs target cell surface antigens upon administration, but engage T cells only after they are activated within the tumor microenvironment (TME). This allows COBRAs to be preferentially turned on in tumors while safely remaining inactive in healthy tissue.

Prospective Randomized Controlled Trial on the Efficacy of Continuous Positive Airway Pressure and Adaptive Servo-Ventilation in the Treatment of Chronic Complex Insomnia.

Background: Complex insomnia, the comorbidity of chronic insomnia and obstructive sleep apnea (OSA), is a common sleep disorder, but the OSA component, whether presenting overtly or covertly, often goes unsuspected and undiagnosed due to a low index of suspicion. Among complex insomniacs, preliminary evidence demonstrates standard CPAP decreases insomnia severity. However, CPAP causes expiratory pressure intolerance or iatrogenic central apneas that may diminish its use.

Sleep disorder prevalence in at-risk adolescents and potential effects of nightmare triad syndrome.

Objective At-risk high school students, those considered to have a higher probability for academic failure or dropping out, were assessed for various sleep disorders. Effects were compared between students with and without the nightmare triad syndrome (NTS+), the sleep disorders' cluster of frequent nightmares, insomnia disorder and suspected sleep-disordered breathing (SDB). Methods Data were gathered at a charter school for at-risk youth using: computer based surveys, physical airway exams, and mental health interviews by school social worker.