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).
View Article and Find Full Text PDFIn the early phase of the COVID-19 pandemic, knowledge about the natural course of recovery of COVID-19 is limited. We therefore describe - based on generic knowledge of post IC syndrome (PICS) and (pulmonary) rehabilitation - the possibilities to organize personalized rehabilitation programs in several care settings. To illustrate variety in need for rehabilitation, we described three cases of critical COVID-19 disease survivors after treatment in the intensive care unit.
View Article and Find Full Text PDFConditionally 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.
View Article and Find Full Text PDFPatients with relapsed or refractory acute myeloid leukemia (AML) have a dismal prognosis and limited treatment options. Chimeric antigen receptor (CAR) T cells have achieved unprecedented clinical responses in patients with B cell leukemias and lymphomas and could prove highly efficacious in AML. However, a significant number of patients with AML may not receive treatment with an autologous product due to manufacturing failures associated with low lymphocyte counts or rapid disease progression while the therapeutic is being produced.
View Article and Find Full Text PDFBackground: Familial hypercholesterolemia (FH) confers a very high risk of premature cardiovascular disease and is commonly caused by mutations in low-density lipoprotein receptor ( apolipoprotein B (), or proprotein convertase subtilisin/kexin type 9 () and very rarely in LDLR adaptor protein 1 () genes.
Objective: To determine the prevalence of pathogenic mutations in the , , and in a cohort of subjects who met Simon Broome criteria for FH and compare the clinical characteristics of mutation-positive and mutation-negative subjects.
Methods: Ninety-three men and 107 women aged 19 to 80 years from lipid clinics in the United States and Canada participated.