Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML

Fujii SI, Kawamata T, Shimizu K, Nakabayashi J, Yamasaki S, Iyoda T, Shinga J, Nakazato H, Sanpei A, Kawamura M, Ueda S, Dörrie J, Mojsov S, Dhodapkar M, Hidaka M, Nojima M, Nagamura F, Yoshida S, Goto T, Tojo A (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Molecular Therapy: Oncolytics Cell Press

Book Volume: 27

Pages Range: 315-332

DOI: 10.1016/j.omto.2022.09.001

Abstract

Strategies integrating activation of innate and adaptive immu-nity against cancer are desired. We established a novel plat-form, Wilms' tumor antigen 1 (WT1)-expressing artificial adjuvant vector cells (aAVC-WT1), linking invariant natural killer T (iNKT)-mediated dendritic cell activation to T cell im-munity. Here, we report the first-in-human application of aAVC-WT1 in nine patients with relapsed and refractory acute myelogenous leukemia. No dose-limiting toxicities were observed, whereas activation of iNKT and/or NK cells was observed in all patients. Five patients experienced objective leukemic regression, which correlated with WT1-specific T cell responses. Paired single-cell RNA and T cell receptor (TCR) sequencing demonstrated effector CD8+ T cell clones in the bone marrow. Some bone marrow CD8+ T cells under-went transition from pre-existing precursor exhausted T cells to functional T cells or emerged as newly activated T cells, some of which were maintained long term. These demonstrate the feasibility and safety of aAVC-WT1 therapy and the capac-ity of this platform to activate both innate and adaptive immu-nity in humans.

Authors with CRIS profile

Jan Dörrie Department of Dermatology

Involved external institutions

National Hospital Organization Kumamoto Medical Center / 熊本医療センター JP Japan (JP) Emory University US United States (USA) (US) Rockefeller University US United States (USA) (US) Riken Institute of Physical and Chemical Research / 理研 JP Japan (JP) Tokyo Medical and Dental University (TMDU) / 東京医科歯科大学 JP Japan (JP) University of Tokyo JP Japan (JP)

How to cite

APA:

Fujii, S.-I., Kawamata, T., Shimizu, K., Nakabayashi, J., Yamasaki, S., Iyoda, T.,... Tojo, A. (2022). Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML. Molecular Therapy: Oncolytics, 27, 315-332. https://dx.doi.org/10.1016/j.omto.2022.09.001

MLA:

Fujii, Shin-Ichiro, et al. "Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML." Molecular Therapy: Oncolytics 27 (2022): 315-332.

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