biostudies-literatureJaime-Ramirez ACNCI NIH HHSNIHNIGMS NIH HHS323-336https://www.ebi.ac.uk/biostudies/studies/S-EPMC4818694biostudies-literatureUnknown4(4)Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F-IgG) could direct innate immune cells with Fc receptors to folate receptor-expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by natural killer (NK) cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased by about 5-fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P< 0.001). F-IgG also enhanced the lysis of chronic lympCancer immunology researchNK Cell-Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines.PMC4818694K24 CA093670P30 CA16058P30 CA016058P01 CA095426T32 CA90338-27CA186542-01A1/PelotoniaF32 CA186542F32 CA186542-01A1K24 CA93670T32 GM068412P01 CA95426T32 GM068412/F32Lee RJButchar JPLu YSkinner CCMao HPhelps MPoi MDavis MLa Perle KMKarpa VLuedke EByrd JCJarjoura DCarson WEMcMichael EPan XLi HSchmitt ACJaime-Ramirez ACLi JMundy-Bosse BLTridandapani SElavazhagan SKondadasula SZhang XRoda JCaligiuri MAJones NBMani AfalseNK Cell-Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines.Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F-IgG) could direct innate immune cells with Fc receptors to folate receptor-expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by natural killer (NK) cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased by about 5-fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P< 0.001). F-IgG also enhanced the lysis of chronic lymp2016-01-01T00:00:00Z2016 Apr2025-04-04T11:59:39.786Z2019-03-27T03:11:02ZS-EPMC48186942686545610.1158/2326-6066.cir-15-016810.1158/2326-6066.CIR-15-0168