{"doi":"10.1093/pnasnexus/pgac244","title":"Intratumoral nanobody–IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice","abstract":"Confining cytokine exposure to the tumors would greatly enhance cancer immunotherapy safety and efficacy. Immunocytokines, cytokines fused to tumor-targeting antibodies, have been developed with this intention, but without significant clinical success to date. A critical limitation is uptake by receptor-expressing cells in the blood, that decreases the dose at the tumor and engenders toxicity. Small-format immunocytokines, constructed with antibody fragments, are hypothesized to improve tumor specificity due to rapid systemic clearance. However, effective design criteria for small-format immunocytokines need further examination. Here, we engineer small interleukin-2 (IL-2) immunocytokines fused to nanobodies with nanomolar to picomolar affinities for the tumor-specific EIIIB domain of fibronectin (also known as EDB). Upon intravenous delivery into immunocompetent mice, such immunocytokines led to similar tumor growth delay as size-matched untargeted IL-2. Intratumoral (i.t.) delivery imparted improved survival dependent on affinity to EIIIB. I.t. administration offers a promising avenue to deliver small-format immunocytokines, given effective affinity for the tumor microenvironment.","journal":"PNAS Nexus","year":2022,"id":244298,"datarank":0.519860385419959,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.0,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":376709,"name":"Noor Jailkhani","orcid":"0000-0002-4933-1068","position":1,"is_corresponding":false},{"id":282790,"name":"Noor Momin","orcid":"0000-0003-3145-6089","position":2,"is_corresponding":false},{"id":877556,"name":"Ying Huang","orcid":"0000-0003-3501-4739","position":3,"is_corresponding":false},{"id":877557,"name":"Allison Sheen","orcid":"0009-0008-6646-260X","position":4,"is_corresponding":false},{"id":626207,"name":"Byong H. Kang","orcid":"0000-0002-1637-2082","position":5,"is_corresponding":false},{"id":314110,"name":"K. Dane Wittrup","orcid":"0000-0003-2398-5896","position":6,"is_corresponding":false},{"id":62838,"name":"Richard O. Hynes","orcid":"0000-0001-7603-8396","position":7,"is_corresponding":false},{"id":618068,"name":"Emi A. Lutz","orcid":"0000-0002-7649-4241","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:25.718788Z","pmid":"36712341","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":[]}