MPC Member Publications

This database contains a listing of population studies publications written by MPC Members. Anyone can add a publication by an MPC student, faculty, or staff member to this database; new citations will be reviewed and approved by MPC administrators.

Full Citation

Title: Anti-NKG2C/IL-15/anti-CD33 Killer Engager Directs Primary and iPSC-derived NKG2C+ NK cells to Specifically Target Myeloid Leukemia

Citation Type: Journal Article

Publication Year: 2021

ISSN: 1525-0016

DOI: 10.1016/J.YMTHE.2021.06.018

Abstract: Natural killer cells mediate cytolysis of transformed cells and are currently used as an adoptive cellular therapy to treat cancer. Infection with human cytomegalovirus has been shown to expand a subset of "adaptive" NK cells, expressing the activation receptor NKG2C, that have preferred functional attributes distinct from conventional NK cells. Because NKG2C delivers a strong activating signal to NK cells, we hypothesized that NKG2C could specifically trigger NK cell-mediated antitumor responses. To elicit a tumor-directed response from NKG2C(+) NK cells, we created an anti-NKG2C/IL-15/anti-CD33 killer engager, called NKG2C-KE, that directs NKG2C(+) cells to target CD33(+) cells, and tumor associated antigen expressed by acute myelogenous leukemia cells. The NKG2C-KE induced specific degranulation, interferon-γ production and proliferation of NKG2C-expressing NK cells from patients who reactivated cytomegalovirus after allogeneic transplantation. The NKG2C-KE was also tested in a more homogeneous system using induced pluripotent stem cell derived NK cells (iNK) that have been engineered to express NKG2C at high levels. The NKG2C-KE triggered iNK cell-mediated cytotoxicity against CD33(+) cells and primary AML blasts. The NKG2C-KE specific interaction with adaptive NK and NKG2C(+) iNK cells represents a new immunotherapeutic paradigm that uniquely engages highly active NK cells to induce cytotoxicity against AML through redirected targeting.

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Authors: Chiu, Emily; Felices, Martin; Cichocki, Frank; Davis, Zachary; Wang, Hongbo; Tuninga, Katie; Vallera, Daniel A.; Lee, Tom; Bjordahl, Ryan; Malmberg, Karl Johan; Valamehr, Bahram; Miller, Jeffrey S.

Periodical (Full): Molecular Therapy

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