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.

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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