Red Blood cells encapsulation of L-Asparaginase Favorably Modulates Target Selectivity and Pharmacodynamics
ASH 2016 Abstract
Enzyme Bioreactors As Drugs
Therapy using erythrocyte-encapsulated enzyme has the advantage of prolonging the half-life of the enzyme and maintaining therapeutic blood levels, reducing the dose and frequency of therapeutic interventions, and preventing the need for expensive chemical modification.
International seminar on thered blood cells as vehicles for drugs
The first human transfusion was performed by the pioneer Dr Jean-Baptiste Denis in France in 1667 and now, three centuries later, around 50 millions blood units are transfused every year, saving millions of lives. Today, there is a new application for red blood cells (RBCs) in cellular therapy: the effective use of erythrocytes as vehicles for chemical or biological drugs. Using this approach, the therapeutic index of RBC-entrapped molecules can be significantly improved with increased efficacy and reduced side effects. This cell-based medicinal product can be manufactured at an industrial scale and is now used in the clinic for different therapeutic applications.
L-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial
l-asparaginase encapsulated within erythrocytes (GRASPA®) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA® for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse.
A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study
The GRASPALL/GRAALL-SA2-2008 Phase II trial evaluated the safety and efficacy of L-asparaginase encapsulated within erythrocytes (GRASP®) in patients ≥ 55 years with Philadelphia chromosome-negative acute lymphoblastic leukemia.
Pancreatic Tumor Sensitivity to Plasma L-Asparagine Starvation
Pancreatic cancer has an overall survival rate of less than 1% at 5 years after diagnosis. That poor outcome is attributable to the difficulty in diagnosing pancreatic cancer at early stages,lack of tumor resectability, and poor response to chemotherapy.
Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma
Asparaginase encapsulated in erythrocytes (eryaspase) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with eryaspase in patients with metastatic PAC.
Can red blood cells prove to be a useful tool in tumor immunotherapy?
Cancer immunotherapy aims to stimulate the patient’s immune system to kill or suppress the tumor. The discovery of tumor-associated antigens (TAAs) has provided important advances in tumor immunology.
Tumor Growth Control Using Red Blood Cells as the Antigen Delivery System and Poly(I:C)
The goal of most current vaccines in tumor immunology is to induce an efficient immune response against the tumor cells. The use of red blood cells (RBCs) for the delivery of tumor-associated antigen to antigen-presenting cells is an innovative approach for cancer immunotherapy.
Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice
Enzyme based therapies therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs.