Format

Send to

Choose Destination
EBioMedicine. 2019 Jan 18. pii: S2352-3964(19)30036-2. doi: 10.1016/j.ebiom.2019.01.031. [Epub ahead of print]

NK cells specifically TCR-dressed to kill cancer cells.

Author information

1
Department of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway.
2
Centre Universitaire Hospitalier Vaudois, University of Lausanne, Lausanne 1011, Switzerland.
3
Department of Core Facilities, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway.
4
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway.
5
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway.
6
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo 0316, Norway.
7
Department of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway. Electronic address: elsin@rr-research.no.
8
Department of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway. Electronic address: sebastw@rr-research.no.

Abstract

BACKGROUND:

Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome.

METHODS:

We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells.

FINDINGS:

This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells.

INTERPRETATION:

These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution. FUND: This work was supported by the Research Council of Norway (#254817), South-Eastern Norway Regional Health Authority (#14/00500-79), by OUS-Radiumhospitalet (Gene Therapy program) and the department of Oncology at the University of Lausanne.

KEYWORDS:

Immunotherapy; Natural killer; T cell; TCR

PMID:
30665853
DOI:
10.1016/j.ebiom.2019.01.031
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science Icon for Norwegian BIBSYS system
Loading ...
Support Center