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Published on: September 3, 2013
Novel prostate cancer immunotherapy with a DNA-encoded anti-prostate-specific membrane antigen monoclonal antibody
Kar Muthumani1, Liron Marnin2, Sagar B Kudchodkar1
1Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA.
Abstract:
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.
Insights
This study introduces a novel DNA-based immunotherapy for prostate cancer, using DNA-encoded monoclonal antibodies (DMAb) targeting prostate-specific membrane antigen (PSMA). This approach effectively controlled tumor growth and improved survival in mice.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Prostate-specific membrane antigen (PSMA) is a key target for prostate carcinoma treatment.
- Current immunotherapies for PSMA have limitations like high costs and short antibody half-life.
Purpose of the Study:
- To develop and evaluate a novel DNA-encoded monoclonal antibody (DMAb) strategy for prostate cancer immunotherapy.
- To assess the efficacy of anti-PSMA DMAb in controlling tumor growth and prolonging survival in a preclinical mouse model.
Main Methods:
- Synthetic DNA plasmids encoding a human anti-PSMA mAb were constructed.
- Electroporation-enhanced intramuscular injection of DMAb plasmids was administered to mice.
- In vivo production of anti-PSMA antibody and its therapeutic effects were analyzed.
Main Results:
- DMAb plasmid injection led to functional and durable anti-PSMA antibody production in vivo.
- The produced anti-PSMA antibody effectively controlled tumor growth and prolonged survival in mice.
- Therapeutic effects were likely mediated by antibody-dependent cellular cytotoxicity (ADCC) involving NK cells.
Conclusions:
- DNA-encoded monoclonal antibody (DMAb) therapy is a promising novel strategy for prostate cancer immunotherapy.
- This approach overcomes limitations of conventional monoclonal antibody therapy.
- Further investigation into DMAb therapy for human prostate cancer and other malignancies is warranted.
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