IL15 Trispecific Killer Engagers (TriKE) Make Natural Killer Cells Specific to CD33+ Targets While Also Inducing Persistence, In Vivo Expansion, and Enhanced Function.

ABSTRACT:

Purpose

The effectiveness of NK cell infusions to induce leukemic remission is limited by lack of both antigen specificity and in vivo expansion. To address the first issue, we previously generated a bispecific killer engager (BiKE) containing single-chain scFv against CD16 and CD33 to create an immunologic synapse between NK cells and CD33(+) myeloid targets. We have now incorporated a novel modified human IL15 crosslinker, producing a 161533 trispecific killer engager (TriKE) to induce expansion, priming, and survival, which we hypothesize will enhance clinical efficacy.

Experimental design

Reagents were tested in proliferation and functional assays and in an in vivo xenograft model of AML.

Results

When compared with the 1633 BiKE, the 161533 TriKE induced superior

SUBMITTER: Vallera DA 

PROVIDER: S-EPMC4947440 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature