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Science. 2016 Jun 10;352(6291):1337-41. doi: 10.1126/science.aaf2288. Epub 2016 May 19.

Targeting of cancer neoantigens with donor-derived T cell receptor repertoires.

Author information

1
Department of Cancer Immunology, Oslo University Hospital Radiumhospitalet, Oslo, Norway. K. G. Jebsen Centers for Cancer Immunotherapy and for Inflammation Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
2
Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
3
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
4
K. G. Jebsen Centers for Cancer Immunotherapy and for Inflammation Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. Department of Immunology and Transfusion Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
5
Department of Cancer Immunology, Oslo University Hospital Radiumhospitalet, Oslo, Norway. K. G. Jebsen Centers for Cancer Immunotherapy and for Inflammation Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. johanna.olweus@medisin.uio.no t.schumacher@nki.nl.
6
Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. johanna.olweus@medisin.uio.no t.schumacher@nki.nl.

Abstract

Accumulating evidence suggests that clinically efficacious cancer immunotherapies are driven by T cell reactivity against DNA mutation-derived neoantigens. However, among the large number of predicted neoantigens, only a minority is recognized by autologous patient T cells, and strategies to broaden neoantigen-specific T cell responses are therefore attractive. We found that naïve T cell repertoires of healthy blood donors provide a source of neoantigen-specific T cells, responding to 11 of 57 predicted human leukocyte antigen (HLA)-A*02:01-binding epitopes from three patients. Many of the T cell reactivities involved epitopes that in vivo were neglected by patient autologous tumor-infiltrating lymphocytes. Finally, T cells redirected with T cell receptors identified from donor-derived T cells efficiently recognized patient-derived melanoma cells harboring the relevant mutations, providing a rationale for the use of such "outsourced" immune responses in cancer immunotherapy.

PMID:
27198675
DOI:
10.1126/science.aaf2288
[Indexed for MEDLINE]
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