BCMA peptide-engineered nanoparticles enhance induction and function of antigen-specific CD8+ cytotoxic T lymphocytes against multiple myeloma: clinical applications.

摘要: The purpose of these studies was to develop and characterize B-cell maturation antigen (BCMA)-specific peptide-encapsulated nanoparticle formulations efficiently evoke BCMA-specific CD8+ cytotoxic T lymphocytes (CTL) with poly-functional immune activities against multiple myeloma (MM). Heteroclitic BCMA72−80 [YLMFLLRKI] liposome or poly(lactic-co-glycolic acid) (PLGA) nanoparticles displayed uniform size distribution increased peptide delivery human dendritic cells, which enhanced induction CTL. Distinct from liposome-based nanoparticles, PLGA-based demonstrated a gradual increase in uptake by antigen-presenting induced CTL higher anti-tumor (CD107a degranulation, proliferation, IFN-γ/IL-2/TNF-α production) primary CD138+ tumor cells MM cell lines. improved functional were associated Tetramer+/CD45RO+ memory CTL, CD28 upregulation on Tetramer+ longer maintenance central (CCR7+ CD45RO+) the highest anti-MM activity less differentiation into effector (CCR7− These results provide framework for therapeutic application BCMA immunogenic peptide system, rather than free peptide, enhance Th1-specific activities. demonstrate potential clinical utility PLGA nanotechnology-based cancer vaccine BCMA-targeted immunotherapy myeloma.