Identification of novel HLA-restricted preferentially expressed antigen in melanoma peptides to facilitate off-the-shelf tumor-associated antigen-specific T-cell therapies |
| |
| Affiliation: | 1. Center for Cancer and Immunology Research, Children''s National Hospital, Washington, DC, USA;2. GW Cancer Center, George Washington University, Washington, DC, USA;3. Division of Blood and Marrow Transplantation, Children''s National Hospital, Washington, DC, USA;4. Division of Allergy and Immunology, Children''s National Hospital, Washington, DC, USA;1. Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA;2. Ben Towne Center for Childhood Cancer Research, Seattle Children''s Research Institute, Seattle, Washington, USA;3. Department of Pediatrics, University of Washington, Seattle, Washington, USA;4. Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, UK;5. Translational Oncology, Allogene Therapeutics, San Francisco, California, USA;6. Department of Medicine, Division of Hematology/Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA;7. Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA;8. Division of Pediatric Hematology/Oncology, Boston Children''s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA;1. Department of Regenerative Technologies and Biofabrication, National Medical Research Radiological Center, Obninsk, Russia;2. Basel University, Basel, Switzerland;1. National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev, Denmark;2. Department of Hematology, Rigshospitalet, Copenhagen, Denmark;1. Program for Cell Enhancement and Technologies for Immunotherapy, Children''s National Medical Center, Washington, DC, USA;2. Institute for Biomedical Sciences, George Washington University, Washington, DC, USA;3. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA;4. National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA |
| |
| Abstract: | Background aimsPreferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen that is overexpressed in many human malignancies and poorly expressed or absent in healthy tissues, making it a good target for anti-cancer immunotherapy. Development of an effective off-the-shelf adoptive T-cell therapy for patients with relapsed or refractory solid tumors and hematological malignancies expressing PRAME antigen requires the identification of major histocompatibility complex (MHC) class I and II PRAME antigens recognized by the tumor-associated antigen (TAA) T-cell product. The authors therefore set out to extend the repertoire of HLA-restricted PRAME peptide epitopes beyond the few already characterized.MethodsPeptide libraries of 125 overlapping 15-mer peptides spanning the entire PRAME protein sequence were used to identify HLA class I- and II-restricted epitopes. The authors also determined the HLA restriction of the identified epitopes.ResultsPRAME-specific T-cell products were successfully generated from peripheral blood mononuclear cells of 12 healthy donors. Ex vivo-expanded T cells were polyclonal, consisting of both CD4+ and CD8+ T cells, which elicited anti-tumor activity in vitro. Nine MHC class I-restricted PRAME epitopes were identified (seven novel and two previously described). The authors also characterized 16 individual 15-mer peptide sequences confirmed as CD4-restricted epitopes.ConclusionsTAA T cells derived from healthy donors recognize a broad range of CD4+ and CD8+ HLA-restricted PRAME epitopes, which could be used to select suitable donors for generating off-the-shelf TAA-specific T cells. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
