{"doi":"10.1016/j.cell.2023.06.002","title":"Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity","abstract":"Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of the antigen recognized by the CAR poses a major obstacle. We found that in vivo vaccine boosting of CAR T cells triggers the engagement of the endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells. This process was accompanied by shifts in CAR T metabolism toward oxidative phosphorylation (OXPHOS) and was critically dependent on CAR-T-derived IFN-γ. Antigen spreading (AS) induced by vaccine-boosted CAR T enabled a proportion of complete responses even when the initial tumor was 50% CAR antigen negative, and heterogeneous tumor control was further enhanced by the genetic amplification of CAR T IFN-γ expression. Thus, CAR-T-cell-derived IFN-γ plays a critical role in promoting AS, and vaccine boosting provides a clinically translatable strategy to drive such responses against solid tumors.","journal":"Cell","year":2023,"id":315191,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":204,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"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":401606,"name":"Alexander Hostetler","orcid":"0000-0001-6260-8765","position":1,"is_corresponding":false},{"id":633121,"name":"Duncan M. Morgan","orcid":"0000-0002-3253-1362","position":2,"is_corresponding":false},{"id":915247,"name":"Laura Maiorino","orcid":"0000-0001-8217-1337","position":3,"is_corresponding":false},{"id":282628,"name":"Ina Sulkaj","orcid":"0000-0002-2494-8942","position":4,"is_corresponding":false},{"id":54226,"name":"Charles A. Whittaker","orcid":"0000-0002-2400-0094","position":5,"is_corresponding":false},{"id":1017131,"name":"Alexandra Neeser","orcid":null,"position":6,"is_corresponding":false},{"id":399197,"name":"Ivan S. Pires","orcid":"0000-0002-4035-0027","position":7,"is_corresponding":false},{"id":528344,"name":"Parisa Yousefpour","orcid":"0000-0003-0431-8131","position":8,"is_corresponding":false},{"id":237695,"name":"Justin M. Gregory","orcid":"0000-0003-2700-0062","position":9,"is_corresponding":false},{"id":1016031,"name":"Kashif Qureshi","orcid":"0009-0002-7734-0567","position":10,"is_corresponding":false},{"id":1016032,"name":"Jonathan Dye","orcid":"0000-0003-2801-8053","position":11,"is_corresponding":false},{"id":239103,"name":"Wuhbet Abraham","orcid":null,"position":12,"is_corresponding":false},{"id":811690,"name":"Heikyung Suh","orcid":"0000-0003-0787-298X","position":13,"is_corresponding":false},{"id":1016033,"name":"Na Li","orcid":"0000-0003-3619-7899","position":14,"is_corresponding":false},{"id":63891,"name":"John Christopher Love","orcid":"0000-0003-0921-3144","position":15,"is_corresponding":false},{"id":236278,"name":"Darrell J. Irvine","orcid":"0000-0002-8637-1405","position":16,"is_corresponding":false},{"id":802140,"name":"Leyuan Ma","orcid":"0000-0002-0583-7470","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T01:06:25.560098Z","pmid":"37413990","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":[]}