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Identification of novel HLA-restricted preferentially expressed antigen in melanoma peptides to facilitate off-the-shelf tumor-associated antigen-specific T-cell therapies.
Stanojevic, Maja; Hont, Amy B; Geiger, Ashley; O'Brien, Samuel; Ulrey, Robert; Grant, Melanie; Datar, Anushree; Lee, Ping-Hsien; Lang, Haili; Cruz, Conrad R Y; Hanley, Patrick J; Barrett, A John; Keller, Michael D; Bollard, Catherine M.
Afiliação
  • Stanojevic M; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Hont AB; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Geiger A; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • O'Brien S; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Ulrey R; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Grant M; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Datar A; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Lee PH; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Lang H; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
  • Cruz CRY; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA; GW Cancer Center, George Washington University, Washington, DC, USA.
  • Hanley PJ; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA; GW Cancer Center, George Washington University, Washington, DC, USA; Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, USA.
  • Barrett AJ; GW Cancer Center, George Washington University, Washington, DC, USA.
  • Keller MD; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA; Division of Allergy and Immunology, Children's National Hospital, Washington, DC, USA.
  • Bollard CM; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA; GW Cancer Center, George Washington University, Washington, DC, USA; Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, USA. Electronic address: cbollard@childrensna
Cytotherapy ; 23(8): 694-703, 2021 08.
Article em En | MEDLINE | ID: mdl-33832817
BACKGROUND AIMS: Preferentially 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. METHODS: Peptide 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. RESULTS: PRAME-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. CONCLUSIONS: TAA 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucócitos Mononucleares / Melanoma Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucócitos Mononucleares / Melanoma Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article