Muthumani et al. developed a synthetic DNA plasmid encoding a PSMA-specific mAb. The in vitro- and/or in vivo-produced therapeutic mAbs bound Fc receptors and mediated ADCC in vitro. In C57BL/6 mice challenged with PSMA-expressing TRAMP-C2 cells, the DNA vaccine suppressed tumor growth and prolonged survival via NK cell-mediated ADCC.
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life. In this report, we describe a novel strategy of antibody-based immunotherapy against prostate carcinoma that utilizes synthetic DNA plasmids that encode a therapeutic human mAb that target PSMA. Electroporation-enhanced intramuscular injection of the DNA-encoded mAb (DMAb) plasmid into mice led to the production of functional and durable levels of the anti-PSMA antibody. The anti-PSMA produced in vivo controlled tumor growth and prolonged survival in a mouse model. This is likely mediated by antibody-dependent cellular cytotoxicity (ADCC) effect with the aid of NK cells. Further study of this novel approach for treatment of human prostate disease and other malignant conditions is warranted.
Author Info: (1) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (2) Department of Pathology and Laboratory Medicine, Perlman School of
Author Info: (1) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (2) Department of Pathology and Laboratory Medicine, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. (3) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (4) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (5) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (6) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (7) Department of Pathology and Laboratory Medicine, Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. (8) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (9) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (10) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. (11) Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA. (12) Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA. (13) Department of Molecular Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, 33612, USA. (14) Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA. (15) Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA. (16) Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA. dweiner@wistar.org.
