The development of a next generation NK cell engager platform by integrating a potency-reduced IL-15 variant to enhance antitumor activity.

ABSTRACT:

Background

Natural killer cell engager (NKCE) has gained attention recently. Conventional NKCEs exhibit mild anti-tumor efficacy despite acceptable safety profiles. Therefore, next-generation NKCE development is essential to enhance efficacy. IL-15, a key NK cell activator, is explored in NKCE design. However, wild-type IL-15 shows significant toxicity in clinical trials. In this study, we present the development of a novel tetravalent NKCE platform (IL15v-NKCE) by incorporating a potency-reduced IL-15 element (IL15v) into our proprietary anti-NKp46 based NKCEs.

Methods

The activity of the IL15v moiety was assessed by quantifying pSTAT5 induction in primary immune cells and evaluating STAT5 activation in an IL-15 reporter cell line. The in vitro activity of IL15v-NKCE

SUBMITTER: Wang L 

PROVIDER: S-EPMC12804171 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature