day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses第四天髓系树突状细胞脉冲与整个肿瘤溶解产物具有免疫原性和引起强大的抗肿瘤反应.pdfVIP

Day-4 Myeloid Dendritic Cells Pulsed with Whole Tumor Lysate Are Highly Immunogenic and Elicit Potent Anti- Tumor Responses 1 1 1 2 Cheryl Lai-Lai Chiang , Andrea R. Hagemann , Rachel Leskowitz , Rosemarie Mick , Thomas 1 3 1 1 1 * Garrabrant , Brian J. Czerniecki , Lana E. Kandalaft , Daniel J. Powell Jr. , George Coukos 1 Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Rena Rowan Breast Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Abstract ‘‘Day-7’’ myeloid DCs are commonly used in the clinic. However, there is a strong need to develop DCs faster that have the same potent immunostimulatory capacity as ‘‘Day-7’’ myeloid DCs and at the same time minimizing time, labor and cost of DC preparations. Although ‘‘2 days’’ DCs can elicit peptide-specific responses, they have not been demonstrated to engulf, process and present complex whole tumor lysates, which could be more convenient and personalized source of tumor antigens than defined peptides. In this preclinical study, we evaluated the T-cell stimulatory capacity of Day-2, Day- 4, and Day-7 cultured monocyte-derived DCs loaded with SKOV3 cell whole lysate prepared by freeze-thaw or by UVB- irradiation followed by freeze-thaw, and matured with lipopolysaccharide (LPS) and interferon (IFN)-gamma. DCs were evaluated for antigen uptake, and following maturation with L