{"doi":"10.1073/pnas.2322356121","title":"IL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines","abstract":"One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 + T cells and ~15-fold increase in the numbers of NK cells at the vaccination site. Notably, with both the model protein antigen OVA as well as various peptide neoantigens, Vax+IL-2cx induced ~5 to 30-fold greater numbers of circulating antigen-specific CD8 + T cells relative to Vax alone. We further demonstrate that Vax+IL-2cx leads to significantly improved efficacy in the MC38 colon carcinoma model relative to either monotherapy alone, driving complete regressions in 50% of mice in a cDC-dependent manner. Relative to vaccine alone, Vax+IL-2cx led to comparable numbers of CD8 + T cells, but markedly greater numbers of NK cells and activated cDCs in the B16F10 melanoma tumor microenvironment post-therapy. Taken together, these findings suggest that the administration of factors that engage both the cDC-CD8 + T cell and cDC-NK cell axes can boost the potency of therapeutic cancer vaccines.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":458805,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1285607,"name":"Laura Cabizzosu","orcid":null,"position":1,"is_corresponding":false},{"id":857027,"name":"Shawn Kang","orcid":null,"position":2,"is_corresponding":false},{"id":1285608,"name":"Kyle T Ruark","orcid":null,"position":3,"is_corresponding":false},{"id":1285609,"name":"Alex J. Najibi","orcid":null,"position":4,"is_corresponding":false},{"id":988295,"name":"Ryan S. Lane","orcid":"0000-0002-6788-3560","position":5,"is_corresponding":false},{"id":1120868,"name":"Einat B. Vitner","orcid":"0000-0001-8578-8551","position":6,"is_corresponding":false},{"id":654076,"name":"Hamza Ijaz","orcid":null,"position":7,"is_corresponding":false},{"id":250234,"name":"Maxence O. Dellacherie","orcid":"0000-0002-2971-2381","position":8,"is_corresponding":false},{"id":1036013,"name":"Mason T. Dacus","orcid":"0000-0002-2192-5382","position":9,"is_corresponding":false},{"id":250235,"name":"Christina M. Tringides","orcid":"0000-0003-2747-1200","position":10,"is_corresponding":false},{"id":841337,"name":"Irene de Lázaro","orcid":"0000-0002-2775-0173","position":11,"is_corresponding":false},{"id":235480,"name":"Mikaël J. Pittet","orcid":"0000-0002-2060-4691","position":12,"is_corresponding":false},{"id":21615,"name":"Sören Müller","orcid":"0000-0001-9490-5270","position":13,"is_corresponding":false},{"id":18142,"name":"Shannon J. Turley","orcid":"0000-0002-0307-908X","position":14,"is_corresponding":false},{"id":65893,"name":"David Mooney","orcid":"0000-0001-6299-1194","position":15,"is_corresponding":false},{"id":252880,"name":"Miguel C. Sobral","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:50.608887Z","pmid":"39556726","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":[]}