CD8 + T cell targeting of tumor antigens presented by HLA-E.

Autor: Iyer RF; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Verweij MC; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Nair SS; Department of Urology and Tisch Cancer Institute, Icahn School of Medicine at Mt Sinai, New York, NY 10029, USA., Morrow D; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Mansouri M; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Chakravarty D; Department of Urology and Tisch Cancer Institute, Icahn School of Medicine at Mt Sinai, New York, NY 10029, USA., Beechwood T; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Meyer C; Vir Biotechnology, San Francisco, CA 14158, USA., Uebelhoer L; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Lauron EJ; Vir Biotechnology, San Francisco, CA 14158, USA., Selseth A; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., John N; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Thin TH; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Dzedzik S; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Havenar-Daughton C; Vir Biotechnology, San Francisco, CA 14158, USA., Axthelm MK; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Douglas J; Vir Biotechnology, San Francisco, CA 14158, USA., Korman A; Vir Biotechnology, San Francisco, CA 14158, USA., Bhardwaj N; Department of Urology and Tisch Cancer Institute, Icahn School of Medicine at Mt Sinai, New York, NY 10029, USA.; Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Tewari AK; Department of Urology and Tisch Cancer Institute, Icahn School of Medicine at Mt Sinai, New York, NY 10029, USA., Hansen S; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Malouli D; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Picker LJ; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA., Früh K; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 May 10; Vol. 10 (19), pp. eadm7515. Date of Electronic Publication: 2024 May 10.
DOI: 10.1126/sciadv.adm7515
Abstrakt: The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E-restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E-restricted CD8 + T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction. Thus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical epitopes. We further demonstrate that PAP-specific, MHC-E-restricted CD8 + T cells from RhCMV/PAP-immunized RM respond to PAP-expressing HLA-E + prostate cancer cells, suggesting that the HLA-E/NKG2A immune checkpoint can be exploited for CD8 + T cell-based immunotherapies.
Databáze: MEDLINE