Description:
Engineering B cells to secrete select antibodies and gene products for the treatment of diseases
Method to produce B cells that can provide prolonged and tunable expression of select antibodies and gene products for the treatment of diseases (for e.g., lysosomal storage diseases)
Several medical disorders are caused by an insufficiency of a gene product or a defective gene product. For example, lysosomal storage diseases are inherited metabolic disorders characterized by lack of sufficient enzymatic activity of lysosomal enzymes leading to abnormal accumulation of specific macromolecules that can lead to organ dysfunction or even organ failure. Enzyme replacement therapy (ERT) can be used as a symptomatic treatment. While beneficial, ERT is cumbersome as it requires patients to have bi-weekly IV infusion of the enzyme for the lifetime of the patient, affecting their quality of life. Thus, better treatment options are needed. To address this, Fred Hutchinson Cancer Center researchers have developed methods to engineer B cells to express a selected antibody and a gene product (secreted and non-secreted). The expression of the gene product is tunable and can be upregulated or downregulated to achieve safe, optimal and prolonged expression of the therapeutic product in-vivo.
<ul>
<li>Treatment of lysosomal disorders (e.g., Gaucher disease, Fabry disease, Pompe disease etc.)</li>
<li>Treatment of clotting disorders (e.g., hemophilia)</li>
<li>Treatment of enzyme deficiencies (e.g., hemolytic anemia/Glucose-6-phosphate dehydrogenase or pyruvate kinase deficiency)</li>
</ul>
<ul>
<li>Obviates the need for biweekly enzyme replacement therapy infusions</li>
<li>Allows for tunable expression (i.e., activation to achieve optimal expression levels of gene product using antigen binding to select antibody engineered in the B cell; and a suicide switch to provide safeguards on expression thresholds)</li>
</ul>
There are nearly 50 lysosomal disorders identified to date and the combined prevalence is about 1 in 7000 live births. The gradual increase in global prevalence of lysosomal storage disorders such as Gaucher, Fabry, Pompe and MPS has been reported. Current SOC is limited to enzyme injections that require bolus administration every few weeks.
<ul>
<li>Justin Taylor Ph.D.; Associate Professor, Vaccine and Infectious Disease Division</li>
</ul>
Preclinical <em>in vitro</em>
Preclinical <em>in vivo</em>
Patent pending
21-207_Taylor_Bcell as source of secreted proteins_NCS_FHCC_Final.pdf
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engineering-B-cells-to-secrete-antibodies-and-gene-products-21-207