A therapeutic against B cell cancers was developed using a novel screening method for rapid drug discovery.
- Screening approach can be used for future drug discovery.
- Therapeutic incorporates cytokine therapy with reduced risk of off-target toxicity.
- Therapeutic is of interest for the treatment of B cell cancers and autoimmune disease.
Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. A promising treatment strategy for leukemia and other cancers is immune cell redirection. This strategy focuses on manipulating anti-cancer immune cells to more precisely target and kill cancer cells while also inducing anti-cancer immune memory. Recently, the FDA approved blinatumomab for the treatment of some patients with B-ALL. Blinatumomab is a fusion protein that links anti-cancer T cells and cancerous B cells. Fusion proteins like this are known as bispecific T cell engagers (BiTE), sometimes referred to as dual-affinity retargeting antibodies (DARTs), or tri-specific T cell activating constructs (TriTACs). Clinical trials for blinatumomab have demonstrated a complete response in 31-34% of adults and 17% of children. A significant proportion of patients relapse with a median post-treatment relapse-free survival time of just 6-8 months, suggesting this treatment can still be improved upon.
Emory inventors developed a treatment strategy that involves concurrent delivery of IL-12, an immune cell-stimulating cytokine, to improve T cell engager activity against leukemic B cells and confer subsequent antileukemic immune memory. Several compounds (BiTEokines) were screened using a rapid library assembly method and two were found to induce higher level (>17 fold) leukemia cell lysis compared to controls. This in vitro proof of concept study supports BiTEokines as a potential B-ALL therapeutic and demonstrates the utility of the rapid library assembly method for future drug discovery.
In vitro proof of concept, studies have been completed. Lead compound optimization and in vivo proof of concept studies are in progress.
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