Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205 Journal Article
| Authors: | Dhodapkar, M. V.; Sznol, M.; Zhao, B.; Wang, D.; Carvajal, R. D.; Keohan, M. L.; Chuang, E.; Sanborn, R. E.; Lutzky, J.; Powderly, J.; Kluger, H.; Tejwani, S.; Green, J.; Ramakrishna, V.; Crocker, A.; Vitale, L.; Yellin, M.; Davis, T.; Keler, T. |
| Article 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. |
| Keywords: | clinical article; controlled study; human tissue; unclassified drug; human cell; fatigue; dose response; drug safety; drug withdrawal; unspecified side effect; colorectal cancer; cancer immunotherapy; melanoma; multiple cycle treatment; ovary cancer; breast cancer; dendritic cell; nausea; myalgia; lung cancer; hemoglobin; tumor regression; bladder cancer; arthralgia; chill; dizziness; drug dose escalation; fever; injection site reaction; sarcoma; feasibility study; cellular immunity; cancer vaccine; antigen specificity; ny eso 1 antigen; immunogenicity; carboxymethylcellulose polycytidylic polyinosinic acid polylysine; flu like syndrome; immunostimulation; drug blood level; phase 1 clinical trial; cancer control; leiomyosarcoma; synovial sarcoma; humoral immunity; transitional cell carcinoma; decreased appetite; cell receptor; resiquimod; human; male; female; priority journal; article; cdx 1401; dec 205 protein; hiltonol |
| Journal Title: | Science Translational Medicine |
| Volume: | 6 |
| Issue: | 232 |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2014-04-16 |
| Start Page: | 232ra51 |
| Language: | English |
| DOI: | 10.1126/scitranslmed.3008068 |
| PROVIDER: | scopus |
| PUBMED: | 24739759 |
| PMCID: | PMC6151129 |
| DOI/URL: | |
| Notes: | Sci. Transl. Med. -- Export Date: 2 June 2014 -- Source: Scopus |
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