title: Antigen-specific TIL therapy for melanoma: A flexible platform for personalized cancer immunotherapy.
abstract: Tumor infiltrating lymphocyte (TIL) therapy has shown objective clinical response rates of 50% in stage IV melanoma patients in a number of clinical trials. Nevertheless, the majority of patients progress either directly upon therapy or after an initial period of tumor control. Recent data have shown that most TIL products that are used for therapy contain only low frequencies of T cells reactive against known melanoma-associated epitopes. Because of this, the development of a technology to create T-cell products that are enriched for reactivity against defined melanoma-associated antigens would seem valuable, both to evaluate the tumoricidal potential of T cells directed against different antigen classes and to potentially increase response rates. Here, we developed and validated a conditional MHC streptamer-based platform for the creation of TIL products with defined antigen reactivities. We have used this platform to successfully enrich both high-frequency (≥1%) and low-frequency (<1%) tumor-specific CD8(+) T-cell populations, and thereby created T-cell products with enhanced tumor recognition potential. Collectively, these data demonstrate that selection of antigen-specific T-cell populations can be used to create defined T-cell products for clinical use. This strategy thus forms a highly flexible platform for the development of antigen-specific cell products for personalized cancer immunotherapy.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kelderman
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fanchi
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Daisy
authors.initials: D
authors.lastname: Philips
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Mireille
authors.initials: M
authors.lastname: Toebes
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Pia
authors.initials: P
authors.lastname: Kvistborg
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Marit M
authors.initials: MM
authors.lastname: van Buuren
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: van Rooij
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Samira
authors.initials: S
authors.lastname: Michels
authors.affiliation: Stage Cell Therapeutics GmbH, Göttingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Germeroth
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: N M
authors.initials: NM
authors.lastname: Schumacher
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D015415:Biomarkers; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods; D011485:Protein Binding; D055503:Protein Multimerization / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
keywords: Antigens ⋅ CD8+ T cells ⋅ Enrichment ⋅ Melanoma ⋅ TIL therapy