title: Targeting of cancer neoantigens with donor-derived T cell receptor repertoires.
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.
authors.affiliation: 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.
authors.forename: Erlend
authors.initials: E
authors.lastname: Strønen
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Mireille
authors.initials: M
authors.lastname: Toebes
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kelderman
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Marit M
authors.initials: MM
authors.lastname: van Buuren
authors.affiliation: 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.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Yang
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: van Rooij
authors.affiliation: Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Marco
authors.initials: M
authors.lastname: Donia
authors.affiliation: 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.
authors.forename: Maxi-Lu
authors.initials: ML
authors.lastname: Böschen
authors.affiliation: 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.
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Lund-Johansen
authors.affiliation: 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.
authors.forename: Johanna
authors.initials: J
authors.lastname: Olweus
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. johanna.olweus@medisin.uio.no t.schumacher@nki.nl.
authors.forename: Ton N
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001782:Blood Donors; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D009154:Mutation; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell