title: CDX-1307: a novel vaccine under study as treatment for muscle-invasive bladder cancer.
abstract: Cancer vaccines have demonstrated clinical benefit, however greater efficacy could be achieved by enhancing their immunogenicity. Owing to cancer vaccines depending on uptake and cross-presentation of tumor antigens by antigen-presenting cells (APCs), we hypothesized that greater immunogenicity would accompany strategies that direct antigen to APC-expressed mannose receptors, initiating a pathway increasing class I and II presentation to T cells. CDX-1307 consists of a human monoclonal antibody targeting the mannose receptor, fused to the human chorionic gonadotropin-β chain (hCG-β), a tumor antigen frequently expressed by epithelial cancers including bladder cancer. In Phase I studies of cancer patients, CDX-1307 was well tolerated and induced significant hCG-β-specific cellular and humoral immune responses when co-administered with GM-CSF and the Toll-like receptor agonists resiquimod and poly-ICLC. An ongoing Phase II trial evaluates CDX-1307 in patients with newly diagnosed, resectable, hCG-β-expressing bladder cancer, where low tumor burden and early intervention may provide greater potential for benefit.
authors.affiliation: Duke University Medical Center, 10 Bryan Searle Drive, 477 Seeley G. Mudd Building, Durham, NC 27710, USA. morse004@mc.duke.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bradley
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Laliberte
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Green
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.forename: Brant A
authors.initials: BA
authors.lastname: Inman
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018997:Chorionic Gonadotropin, beta Subunit, Human; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins