{"doi":"10.21203/rs.3.rs-993445/v1","title":"A programmable bispecific nano-immuno-engager promotes T cell homing and reprograms tumour microenvironment","abstract":"Abstract Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective homing of T effector (T eff ) cells to tumours and the immunosuppressive tumour microenvironment (TME). Here, we report a programmable tumour cells/T eff cells bispecific nano-immuno-engager (NIE) that can circumvent these limitations to improve ICB therapy. We have developed 28 nm non-toxic peptidic micellar nanoparticles (NIE-NPs) that bind α 3 β 1 integrin on tumour cells membrane and undergo in situ transformation on surface of tumour cells into nanofibrillar network (NIE-NFs). The nanofibrillar network persistently facilitates cytotoxic T cells’ homing to the proximity of tumour cells via activatable α 4 β 1 integrin ligands, and also allows sustained release of resiquimod to reprogram the TME. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.","journal":"Research Square","year":2021,"id":227868,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9448,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":464366,"name":"Ruonan Bo","orcid":null,"position":1,"is_corresponding":false},{"id":832173,"name":"Yi Wu","orcid":"0000-0002-4955-3533","position":2,"is_corresponding":false},{"id":464367,"name":"Longmeng Li","orcid":null,"position":3,"is_corresponding":false},{"id":832174,"name":"Zheng Zhu","orcid":"0000-0002-5842-5832","position":4,"is_corresponding":false},{"id":381826,"name":"Ai‐Hong Ma","orcid":"0000-0001-9798-164X","position":5,"is_corresponding":false},{"id":237442,"name":"Wenwu Xiao","orcid":"0000-0003-0387-7206","position":6,"is_corresponding":false},{"id":832175,"name":"Yanyu Huang","orcid":"0000-0002-4134-944X","position":7,"is_corresponding":false},{"id":237439,"name":"Tatu Rojalin","orcid":"0000-0002-9805-1353","position":8,"is_corresponding":false},{"id":832176,"name":"Xingbin Yin","orcid":"0000-0003-3077-1626","position":9,"is_corresponding":false},{"id":76180,"name":"Yongheng Wang","orcid":"0000-0003-4442-0747","position":10,"is_corresponding":false},{"id":381828,"name":"Hongyong Zhang","orcid":"0000-0002-5669-5791","position":11,"is_corresponding":false},{"id":832177,"name":"Kelmen Low","orcid":"0000-0001-5155-0158","position":12,"is_corresponding":false},{"id":832687,"name":"Kiana Lee","orcid":null,"position":13,"is_corresponding":false},{"id":524404,"name":"Yousif Ajena","orcid":null,"position":14,"is_corresponding":false},{"id":563723,"name":"Jing Di","orcid":"0000-0001-5637-8748","position":15,"is_corresponding":false},{"id":832178,"name":"Dalin Zhang","orcid":"0000-0003-0346-7020","position":16,"is_corresponding":false},{"id":832688,"name":"Chris Baehr","orcid":null,"position":17,"is_corresponding":false},{"id":310038,"name":"Ruiwu Liu","orcid":null,"position":18,"is_corresponding":false},{"id":237447,"name":"Lei Wang","orcid":"0000-0003-1405-9815","position":19,"is_corresponding":false},{"id":237446,"name":"Yuanpei Li","orcid":"0000-0002-4015-646X","position":20,"is_corresponding":false},{"id":237448,"name":"Kit S. Lam","orcid":"0000-0002-3076-6969","position":21,"is_corresponding":false},{"id":237436,"name":"Lu Zhang","orcid":"0000-0002-7492-6047","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:46.312854Z","pmid":null,"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":[]}