title: Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205.
abstract: Immune-based therapies for cancer are generating substantial interest because of the success of immune checkpoint inhibitors. This study aimed to enhance anticancer immunity by exploiting the capacity of dendritic cells (DCs) to initiate T cell immunity by efficient uptake and presentation of endocytosed material. Delivery of tumor-associated antigens to DCs using receptor-specific monoclonal antibodies (mAbs) in the presence of DC-activating agents elicits robust antigen-specific immune responses in preclinical models. DEC-205 (CD205), a molecule expressed on DCs, has been extensively studied for its role in antigen processing and presentation. CDX-1401 is a vaccine composed of a human mAb specific for DEC-205 fused to the full-length tumor antigen NY-ESO-1. This phase 1 trial assessed the safety, immunogenicity, and clinical activity of escalating doses of CDX-1401 with the Toll-like receptor (TLR) agonists resiquimod (TLR7/8) and Hiltonol (poly-ICLC, TLR3) in 45 patients with advanced malignancies refractory to available therapies. Treatment induced humoral and cellular immunity to NY-ESO-1 in patients with confirmed NY-ESO-1-expressing tumors across various dose levels and adjuvant combinations. No dose-limiting or grade 3 toxicities were reported. Thirteen patients experienced stabilization of disease, with a median duration of 6.7 months (range, 2.4+ to 13.4 months). Two patients had tumor regression (~20% shrinkage in target lesions). Six of eight patients who received immune-checkpoint inhibitors within 3 months after CDX-1401 administration had objective tumor regression. This first-in-human study of a protein vaccine targeting DCs demonstrates its feasibility, safety, and biological activity and provides rationale for combination immunotherapy strategies including immune checkpoint blockade.
authors.affiliation: Yale Cancer Center, New Haven, CT 06520, USA.
authors.forename: Madhav V
authors.initials: MV
authors.lastname: Dhodapkar
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
authors.forename: Biwei
authors.initials: B
authors.lastname: Zhao
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.forename: Mary L
authors.initials: ML
authors.lastname: Keohan
authors.forename: Ellen
authors.initials: E
authors.lastname: Chuang
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sanborn
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.forename: John
authors.initials: J
authors.lastname: Powderly
authors.forename: Harriet
authors.initials: H
authors.lastname: Kluger
authors.forename: Sheela
authors.initials: S
authors.lastname: Tejwani
authors.forename: Jennifer
authors.initials: J
authors.lastname: Green
authors.forename: Venky
authors.initials: V
authors.lastname: Ramakrishna
authors.forename: Andrea
authors.initials: A
authors.lastname: Crocker
authors.forename: Laura
authors.initials: L
authors.lastname: Vitale
authors.forename: Michael
authors.initials: M
authors.lastname: Yellin
authors.forename: Thomas
authors.initials: T
authors.lastname: Davis
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D016207:Cytokines; C093569:DEC-205 receptor; D000939:Epitopes; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D007371:Interferon-gamma
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