NY-ESO-1 peptides/threitolceramide-6-loaded nanoparticles PORT-3

An immunomodulating agent and nanovaccine composed of the invariant natural killer T-cell (iNKT) agonist, dendritic cell (DC) transactivator, and an alpha-galactosylceramide (a-GalCer) analog threitolceramide-6 (ThrCer6, IMM60) and immunogenic peptides derived from the tumor-associated antigen (TAA) New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanoparticles, with potential immunomodulating and antineoplastic activities. Upon administration of NY-ESO-1 peptides/ThrCer6-loaded nanoparticles PORT-3, ThrCer6 targets and binds to the T-cell receptor on iNKTs, thereby activating the iNKTs. The activated iNKTs activate DCs, resulting in the secretion of a large amount of pro-inflammatory cytokines. The NY-ESO-1 peptides are processed and presented by DCs. Altogether, this induces antigen-specific CD4 and CD8 T-cell, and B-cell responses, and leads to the induction of a cytotoxic T-lymphocyte (CTL)-mediated immune response against NY-ESO-1-expressing tumor cells. Encapsulating antigens and adjuvants together within the same biodegradable polymeric nanoparticle can enhance T-cell responses. NY-ESO-1 is a cancer-testis antigen normally expressed in testicular germ cells and trophoblasts of the placenta and overexpressed in a variety of cancers.