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Natural Killer Cell Function Activated by CD19-Targeted Molecule in CLL

By: Sarah Campen, PharmD
Posted: Thursday, August 1, 2019

Researchers at the University of Minnesota have developed a novel CD19-targeting trispecific killer engager (TriKE) molecule that appears to redirect natural killer cell function against tumor cells in chronic lymphocytic leukemia (CLL). The agent, 161519 TriKE, drives an activating and proliferative signal on natural killer cells, resulting in enhanced natural killer cell expansion and CLL target killing. The results of their research were published in Blood Advances.

“Our findings indicate the potential immunotherapeutic value of 161519 TriKE in CLL,” explained Martin Felices, PhD, of the Department of Medicine at the University of Minnesota, Minneapolis, and colleagues. “By triggering an endogenous [natural killer] cell response, which displays a less toxic profile than T-cell responses, 161519 TriKE offers a potentially valuable off-the-shelf alternative to [chimeric antigen receptor] T-cell therapies that could be used alone or in combination with adoptive [natural killer] cell therapy.”

When evaluating the priming effect of the interleukin-15 (IL-15) moiety in 161519 TriKE on natural killer cell activation, Dr. Felices and colleagues discovered that 161519 TriKE induced a significant increase in natural killer cell degranulation. They measured a higher proportion of CD107a-expressing cells and at least a 3.5-fold increase in interferon gamma–producing natural killer cells with 161519 TriKE when compared with rituximab or IL-15 alone.

The IL-15 moiety on 161519 TriKE triggered robust proliferation of natural killer cells, with activity similar to equifunctional monomeric IL-15. The novel agent also induced superior directed killing of a CD19-expressing Burkitt’s lymphoma cell line when compared with rituximab. “We propose that 161519 TriKE should be further evaluated as a treatment of refractory CLL patients in settings where there are no satisfactory therapeutic alternatives,” concluded the researchers.

Disclosure: The study authors’ disclosure information may be found at bloodadvances.org.



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