Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab
| Autor: | Stanley R. Riddell, Ernesto Iaccucci, Jonathan Zalevsky, Kelly G. Paulson, Joshua R. Veatch, Scott S. Tykodi, Naina Singhi, Brenda Jesernig |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research T-Lymphocytes T cell Immunology Autoantigens Young Adult 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Humans Immunology and Allergy Melanoma RC254-282 Pharmacology integumentary system business.industry Correction Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Immune checkpoint Nivolumab 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Cancer/testis antigens business CD8 |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 8, Iss 2 (2020) J Immunother Cancer |
| ISSN: | 2051-1426 |
| Popis: | T cells that recognize self-antigens and mutated neoantigens are thought to mediate antitumor activity of immune checkpoint blockade (ICB) in melanoma. Few studies have analyzed self and neoantigen-specific T cell responses in patients responding to ICB. Here, we report a patient with metastatic melanoma who had a durable clinical response after treatment with the programmed cell death protein 1 inhibitor, nivolumab, combined with the first-in-class CD122-preferential interleukin-2 pathway agonist, bempegaldesleukin (BEMPEG, NKTR-214). We used a combination of antigen-specific T cell expansion and measurement of interferon-γ secretion to identify multiple CD4+ and CD8+ T cell clones specific for neoantigens, lineage-specific antigens and cancer testis antigens in blood and tumor from this patient prior to and after therapy. Polyclonal CD4+ and CD8+ T cells specific to multiple neoantigens but not self-antigens were highly enriched in pretreatment tumor compared with peripheral blood. Neoantigen, but not self-antigen-specific T cell clones expanded in frequency in the blood during successful treatment. There was evidence of dramatic immune infiltration into the tumor on treatment, and a modest increase in the relative frequency of intratumoral neoantigen-specific T cells. These observations suggest that diverse CD8+ and CD4+ T cell clones specific for neoantigens present in tumor before treatment had a greater role in immune tumor rejection as compared with self-antigen-specific T cells in this patient. Trial registration number: NCT02983045. |
| Databáze: | OpenAIRE |
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