{"doi":"10.1136/jitc-2020-001591","title":"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","abstract":"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 .","journal":"Journal for ImmunoTherapy of Cancer","year":2020,"id":84787,"datarank":0.5466236387465864,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.20123587479747948,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.20123587479747948,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":8,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.945,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02983045"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":434373,"name":"Naina Singhi","orcid":"0000-0001-8431-1823","position":1,"is_corresponding":false},{"id":435117,"name":"Brenda L. Jesernig","orcid":null,"position":2,"is_corresponding":false},{"id":434374,"name":"Kelly G. Paulson","orcid":"0000-0002-0033-3708","position":3,"is_corresponding":false},{"id":285138,"name":"Jonathan Zalevsky","orcid":"0000-0003-2707-1709","position":4,"is_corresponding":false},{"id":435118,"name":"Ernesto Iacucci","orcid":null,"position":5,"is_corresponding":false},{"id":232506,"name":"Scott S. Tykodi","orcid":"0000-0002-0399-0965","position":6,"is_corresponding":false},{"id":232699,"name":"Stanley R. Riddell","orcid":"0000-0002-4688-9920","position":7,"is_corresponding":false},{"id":434372,"name":"Joshua Veatch","orcid":"0000-0002-6543-9255","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-18T21:55:38.506333Z","pmid":"33298619","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}