EFFECTS OF BRYOSTATIN ON NATURAL KILLER CELLS ALONE OR IN COMBINATION WITH INTERLEUKIN-12

Abstract

We investigated a possible new approach towards enhancing the immune response. We generated mRNA expression profiles upon treatment of the natural killer 92 (NK92) cell line with individual agents in comparison to treatment with two agents at the same time. The NK cells were either untreated, treated with interleukin-12 (IL-12), phorbol myristic acetate (PMA), bryostatin, or a combination of PMA + IL-12 or bryostatin + IL-12. mRNA from each treatment was converted to labeled cDNA and hybridized to oligonucleotide microarrays for measuring gene expression. Measurements from arrays and Q-PCR determined which genes might be potential biomarkers for bryostatin + IL-12 or bryostatin compared to PMA. These genes were RRM2B, TBCD2B, PLAU, LIMA1, CCR1, SPRED2 and FHOD1.. Analysis of functional terms in the Gene Ontology (GO) database for both bryostatin and bryostatin. + IL-12 treatments revealed good evidence that cells were active and proliferating, crucial for NK cell-based immunotherapy.