{"doi":"10.3390/cancers14081930","title":"CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies","abstract":"The macrophage checkpoint interaction CD47-SIRPα is an emerging target for cancer therapy, but clinical trials of monoclonal anti-CD47 show efficacy only in liquid tumors when combined with tumor-opsonizing IgG. Here, in challenging metastatic solid tumors, CD47 deletion shows no effect on tumor growth unless combined with otherwise ineffective tumor-opsonization, and we likewise show wild-type metastases are suppressed by SIRPα-blocked macrophages plus tumor-opsonization. Lung tumor nodules of syngeneic B16F10 melanoma cells with CD47 deletion show opsonization drives macrophage phagocytosis of B16F10s, consistent with growth versus phagocytosis calculus for exponential suppression of cancer. Wild-type CD47 levels on metastases in lungs of immunocompetent mice and on human metastases in livers of immunodeficient mice show that systemic injection of antibody-engineered macrophages also suppresses growth. Such in vivo functionality can be modulated by particle pre-loading of the macrophages. Thus, even though CD47-SIRPα disruption and tumor-opsonizing IgG are separately ineffective against established metastatic solid tumors, their combination in molecular and cellular therapies prolongs survival.","journal":"Cancers","year":2022,"id":258533,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344177,"name":"Lawrence J. Dooling","orcid":"0000-0002-1688-2066","position":1,"is_corresponding":false},{"id":382767,"name":"Michael P. Tobin","orcid":"0000-0002-9607-2062","position":2,"is_corresponding":false},{"id":910099,"name":"William W. Zhang","orcid":"0000-0002-1426-9698","position":3,"is_corresponding":false},{"id":910100,"name":"Brandon H. Hayes","orcid":"0000-0001-6778-0548","position":4,"is_corresponding":false},{"id":346222,"name":"Justine Y. Lee","orcid":null,"position":5,"is_corresponding":false},{"id":246141,"name":"Xiaoling Jin","orcid":"0000-0003-1277-2844","position":6,"is_corresponding":false},{"id":506157,"name":"Jerome Irianto","orcid":"0000-0002-4804-7225","position":7,"is_corresponding":false},{"id":7873,"name":"Dennis E. Discher","orcid":"0000-0001-6163-2229","position":8,"is_corresponding":false},{"id":273727,"name":"Jason C. Andrechak","orcid":"0000-0002-6659-9488","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:25:43.037820Z","pmid":"35454837","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":[]}