cell-based immunotherapies has tremendous potential for treating various diseases, such as cancer or suppress the immune activating in autoimmune diseases. Most cell-based cancer immunotherapies in clinical adjuvant signaling through genetic engineering to improve the function of T cells, however, are genetically encoded signals have minimal control over the dosage and last for the life of cell lineages.
These properties make it difficult to balance the increase in therapeutic efficacy with reduced toxicity. Here, we demonstrate the potential ligand-coupled phospholipids as non-genetic system for the engineering of immune cells. This system provides a simple, controlled, non-genetic adjuvant delivery cells through insertion immune-mediated lipid in the plasma membrane.
Lipid-mediated insertion (called depoting) successfully sent Toll-like receptor (TLR) ligands to cell surface and intracellular immune cells are mixed. This ligand depoted into immune cells in a dose-controlled fashion and did not compete during the pairs multiplex loading. activation of immune cells can be enhanced by autocrine and paracrine mechanisms depending on the biology of TLR ligands tested.
Depoted functional ligand survive in the plasma membrane of up to 4 days in naive and activated T cells, increase their activation, proliferation, and cytokine secretion skewing. Our data suggest that adjuvant ligand depoted signaling persistent but non-permanent for immune cells that can minimize the intensity and duration of toxicity compared to permanent genetic delivery. Overall, the findings suggest the potential for lipid-mediated depoting as a universal cell engineering approaches with unique, complementary advantages for other cell engineering methods.
Lipid-Mediated Insertion of Toll-Like Receptor (TLR) Ligands for Facile Immune Cell Engineering
A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 (TLR 7) Agonist (RO7020531) in Chinese Healthy Volunteers.
TLR7 agonists modulate the activity of the immune broad spectrum and evaluated in the treatment of human diseases including cancer and chronic viral infections. RO7020531, a prodrug orally from agonist TLR7, is in clinical development as part of a regimen of curative against chronic hepatitis B. We report the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7020531 in healthy volunteers of China following single and multiple dose ascending (SAD and MAD). PK and PD samples were evaluated from four cohorts of a three cohort SAD and MAD with 10 subjects each (8 active, 2 placebo). Safety and tolerability were monitored throughout the study. A total of 155 adverse events (AEs) were reported in 49 subjects. Fifty-one AE in 18 subjects were assessed as related to treatment. Most AEs were mild; nine subjects experienced moderate AE; no severe AEs.
In two cohorts of 150 mg given daily MAD (qod), 7 of the 20 subjects who experienced fever and asymptomatic temporarily halted because lymphopenia, completed 24-48 hours post-dose. PK of the active metabolite, RO7011785, increased linearly with doses of 40mg to 170mg. No accumulation following PK dose qod. PK profile consistent with observations in white subjects in the first study of human-in-global. single and multiple doses of RO7020531 resulted in dose-dependent increase in markers of response to TLR7 or above 100mg.
Description: A sandwich ELISA for quantitative measurement of Rat Toll Like Receptor4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Toll Like Receptor4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Toll Like Receptor4 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 3 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 2 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 2 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 2 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 7 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 7 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 7 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 8 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 8 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 8 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 9 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 9 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 9 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 5 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 5 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 5 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 6 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 6 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Toll Like Receptor 6 in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Toll Like Receptor 2 (TLR2) in samples from tissue homogenates, cell lysates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Toll Like Receptor 2 (TLR2) in samples from tissue homogenates, cell lysates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Toll Like Receptor 4 (TLR4) in samples from tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Toll Like Receptor 4 (TLR4) in samples from tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Flu-like symptoms associated with interferon-α levels were higher. RO7020531 safe and well tolerated in healthy volunteers received China with multiple dose regimen of 150 mg qod.
No Comment