{"doi":"10.17615/t2eg-ws81","title":"Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib","abstract":"Graft-versus-host disease (GVHD) represents a major hurdle impeding the efficacy of allogeneic bone marrow transplantation (BMT). Bortezomib is a proteasome inhibitor that was recently approved for treatment of myeloma. We found that bortezomib potently inhibited in vitro mixed lymphocyte responses and promoted the apoptosis of alloreactive T cells. Bortezomib given at the time of allogeneic BMT in mice resulted in significant protection from acute GVHD. Reductions in GVHD-associated parameters and biological evidence of proteasome inhibition were observed with this regimen but with no adverse effects on long-term donor reconstitution. Assessment of graft-versus-tumor responses in advanced leukemia-bearing mice demonstrated that only the combination of allogeneic BMT and T cells with bortezomib promoted significant increases in survival. Increased cytotoxic T cell killing of the tumor was also observed. Thus, the combination of proteasome inhibition with selective immune attack can markedly increase the efficacy of BMT in cancer.","journal":"UNC Libraries","year":2020,"id":114440,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":538642,"name":"W. J. Murphy","orcid":null,"position":1,"is_corresponding":false},{"id":538643,"name":"R. Sitcheran","orcid":null,"position":2,"is_corresponding":false},{"id":538644,"name":"B. R. Blazar","orcid":null,"position":3,"is_corresponding":false},{"id":538645,"name":"I. Barao","orcid":null,"position":4,"is_corresponding":false},{"id":538646,"name":"J. S. Serody","orcid":null,"position":5,"is_corresponding":false},{"id":538647,"name":"L. A. Welniak","orcid":null,"position":6,"is_corresponding":false},{"id":537974,"name":"Matthew J. O’Shaughnessy","orcid":"0000-0001-6380-0839","position":7,"is_corresponding":false},{"id":538648,"name":"W. Riordan","orcid":null,"position":8,"is_corresponding":false},{"id":488197,"name":"Angela Panoskaltsis‐Mortari","orcid":"0000-0003-1802-1785","position":9,"is_corresponding":false},{"id":538649,"name":"C. Wysocki","orcid":null,"position":10,"is_corresponding":false},{"id":20830,"name":"K. Sun","orcid":null,"position":11,"is_corresponding":false},{"id":538650,"name":"T. J. Sayers","orcid":null,"position":12,"is_corresponding":false},{"id":9453,"name":"H. Liu","orcid":"0000-0003-4570-4514","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:29.674622Z","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":[]}