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Alnylam, Collaborators Report on RNAi Enhancement of Dendritic Cancer Cell Vaccine

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Alnylam Pharmaceuticals last week published preclinical data describing the development of a dendritic cell cancer vaccine enhanced with RNAi.

According to the company, its researchers and collaborators from Radboud University Nijmegen Medical Centre designed siRNAs toward PD-L1 and PD-L2, which are “key co-inhibitory proteins expressed on antigen-presenting cells that strongly limit activation of T-cells needed for a potent immune response to the tumor.”

“Lipid nanoparticle-formulated siRNA targeting PD-L1 and PD-L2 mediated efficient and specific silencing of PD-L1 and PD-L2 expression on human monocyte-derived [dendritic cells] isolated from healthy donors,” Alnylam said in a statement. “Ex vivo treatment with siRNA was well tolerated by the isolated [cells], with no measurable effect on phenotype or migratory capacity.”

Dendritic cells treated with the siRNAs were loaded with mRNA encoding minor histocompatibility antigen to allow “long-lasting presentation of antigenic peptides expressed by malignant cells,” it added. “The resulting PD-L silenced, MiHA-expressing DCs were shown to have a significantly enhanced ability to stimulate antigen-specific CD8+ T cell responses in cells from transplanted cancer patients ex vivo.”

The findings appeared online last week in Cancer Immunology Immunotherapy.

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