• University of Michigan-Ann Arbor (2015)

  • Immunology

  • Todd A. Fehniger, M.D., Ph.D.

  • Molecular mechanisms of cytokine-induced memory-like NK cell differentiation

  • Jennifer.tran@wustl.edu

Research

Natural killer (NK) cells are innate lymphoid cells that are crucial for host defense from viral infections and tumor cells. The ability of NK cells to recognize and kill malignant cells provides a strong premise to advance them as a cellular therapy in the clinical setting. While NK cell-based therapies are being explored in clinical trials, issues with persistence and in vivo functionality have been identified as limitations to their clinical application. Our lab pioneered cytokine-induced memory-like (ML) NK cells that are generated after brief activation with IL-12, IL-15, and IL-18. This overcomes many of the shortcomings of conventional NK cells as a cellular therapy. ML NK cells exhibited enhanced functionality, cytotoxicity, and persistence in a phase I clinical trial for acute myeloid leukemia (AML), with many patients achieving complete remissions from this novel intervention. Despite the translational advancement, there is little known about the underlying mechanisms of ML programming in NK cells. Clarifying the molecular programs that drive the ML phenotype will have broad implications for optimizing NK cells as a cellular-based therapy for hematological malignancies.

Graduate Publications:

Berrien-Elliott MM, Foltz JA, Russler-Germain DA, Neal CC, Tran J, Gang M, Wong P, Fisk B, Cubitt CC, Marin ND, Zhou AY, Jacobs MT, Foster M, Schappe T, McClain E, Kersting-Schadek S, Desai S, Pence P, Becker-Hapak M, Eisele J, Mosior M, Marsala L, Griffith OL, Griffith M, Khan SM, Spencer DH, DiPersio JF, Romee R, Uy GL, Abboud CN, Ghobadi A, Westervelt P, Stockerl-Goldstein K, Schroeder MA, Wan F, Lie WR, Soon-Shiong P, Petti AA, Cashen AF, Fehniger TA. 2022 Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Sci Transl Med, 14(633):eabm1375.

Marin ND, Krasnick BA, Becker-Hapak M, Conant L, Goedegebuure SP, Berrien-Elliott MM, Robbins KJ, Foltz JA, Foster M, Wong P, Cubitt CC, Tran J, Wetzel CB, Jacobs M, Zhou A, Russler-Germain D, Marsala L, Schappe T, Fields RC, Fehniger TA. 2021 Memory-like differentiation enhances NK cell responses to melanoma. Clin Cancer Res, 27(17):4859-69.

Becker-Hapak MK, Shrestha N, McClain E, Dee MJ, Chaturvedi P, Leclerc GM, Marsala LI, Foster M, Schappe T, Tran J, Desai S, Neal CC, Pence P, Wong P, Wagner JA, Russler-Germain D, Zhu X, Spanoudis CM, Gallo VL, Echeverri CA, Ramirez LL, You L, Egan JO, Rhode PR, Jiao JA, Muniz GJ, Jeng EK, Prendes CA, Sullivan RP, Berrien-Elliott MM, Wong HC, Fehniger TA. 2021 A fusion protein complex that combines IL12, IL15, and IL18 signaling to induce memory-like NK cells for cancer immunotherapy. Cancer Immunol Res, 9(9):1071-87.

Gang M, Marin ND, Wong P, Neal CC, Marsala L, Foster M, Schappe T, Meng W, Tran J, Schaettler M, Davila ML, Gao F, Cashen AF, Bartlett NL, Mehta-Shah N, Kahl B, Kim M, Cooper ML, DiPersio JF, Berrien-Elliott MM, Fehniger TA. 2020 CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas. Blood, 136(20):2308-2318.

Last Updated: 8/1/2022 9:32:40 AM

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