Anticancer immunity may be enhanced by harnessing the ability of dendritic cells to initiate T-cell immunity through efficient uptake and presentation of endocytosed material. In preclinical models, delivery of tumor-associated antigens to dendritic cells using receptor-specific monoclonal antibodies in the presence of dendritic cell–activating agents has produced marked antigen-specific immune responses.
CDX-1401 is a vaccine consisting of a monoclonal antibody specific for DEC-205, a molecule expressed on dendritic cells that is active in antigen processing and presentation, fused to the full-length tumor antigen NY-ESO-1. In a phase I trial reported in Science Translational Medicine, Dhodapkar and colleagues assessed the safety, immunogenicity, and clinical activity of escalating doses of CDX-1401 along with administration of Toll-like receptor (TLR) agonists resiquimod (TLR7/8) and Hiltonol (poly-ICLC, TLR3) in 45 patients with advanced malignancies refractory to available therapies.
Vaccine was associated with humoral and cellular immunity to NY-ESO-1 in patients with NY-ESO-1–expressing tumors across various dose levels and adjuvant combinations. No dose-limiting or grade 3 toxicities were reported. Stable disease was observed in 13 patients, with a median duration of 6.7 months (range = 2.4+ to 13.4 months), and 2 patients had approximately 20% shrinkage in target lesions. Six of eight patients who received TLR inhibitors within 3 months after vaccine administration had objective tumor regression.
The investigators concluded, “This first-in-human study of a protein vaccine targeting [dendritic cells] demonstrates its feasibility, safety, and biological activity and provides rationale for combination immunotherapy strategies including immune checkpoint blockade.” ■
Dhodapkar NV, et al: Sci Transl Med 6:232ra51, 2014.
Lab Notes is compiled and written for The ASCO Post by Matthew Stenger.
