{"doi":"10.3389/fimmu.2023.1072810","title":"Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo","abstract":"Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress in vivo melanoma proliferation and induced significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rβ/γ binding and attenuated but preserved IL-2Rα binding, induced lower systemic cytokine activation with non-inferior protection in murine tumor studies. Transcriptomic analyses demonstrated an upregulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer.","journal":"Frontiers in Immunology","year":2023,"id":363584,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353685,"name":"Ziyang Xu","orcid":"0000-0001-7690-7029","position":1,"is_corresponding":false},{"id":1118467,"name":"Michaela Helble","orcid":null,"position":2,"is_corresponding":false},{"id":353687,"name":"Susanne N. Walker","orcid":"0000-0002-0034-5362","position":3,"is_corresponding":false},{"id":332103,"name":"Kevin Liaw","orcid":"0000-0002-8235-1407","position":4,"is_corresponding":false},{"id":353686,"name":"Neethu Chokkalingam","orcid":"0000-0001-7165-4544","position":5,"is_corresponding":false},{"id":443264,"name":"Toshitha Kannan","orcid":"0009-0007-7775-6585","position":6,"is_corresponding":false},{"id":816501,"name":"Yuanhan Wu","orcid":"0000-0002-4706-439X","position":7,"is_corresponding":false},{"id":353688,"name":"Edgar Tello‐Ruiz","orcid":"0000-0001-7352-4866","position":8,"is_corresponding":false},{"id":701120,"name":"Daniel H. Park","orcid":"0000-0002-2773-320X","position":9,"is_corresponding":false},{"id":353690,"name":"Xizhou Zhu","orcid":"0000-0002-3646-6668","position":10,"is_corresponding":false},{"id":331747,"name":"Megan C. Wise","orcid":"0000-0001-5663-4916","position":11,"is_corresponding":false},{"id":461096,"name":"Trevor R.F. Smith","orcid":"0000-0002-0671-2565","position":12,"is_corresponding":false},{"id":348470,"name":"Sonali Majumdar","orcid":"0000-0002-6574-8787","position":13,"is_corresponding":false},{"id":245076,"name":"Andrew V. Kossenkov","orcid":"0000-0002-1536-0418","position":14,"is_corresponding":false},{"id":237272,"name":"Daniel W. Kulp","orcid":"0000-0002-0527-3804","position":15,"is_corresponding":false},{"id":331754,"name":"David B. Weiner","orcid":"0000-0002-2232-8512","position":16,"is_corresponding":false},{"id":467016,"name":"Nicholas J. Tursi","orcid":"0000-0001-6752-3402","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:32.510714Z","pmid":"36911698","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":[]}