Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

BMC Cancer. 2014 Jan 18:14:30. doi: 10.1186/1471-2407-14-30.


Background: Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer.

Methods: We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student's t-test), proliferation (paired Student's t-test), CD107a expression (paired Student's t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves).

Results: PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice.

Conclusions: Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Cell Degranulation
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • GPI-Linked Proteins / immunology
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / immunology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / biosynthesis*
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Fusion Proteins / biosynthesis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Time Factors
  • Transduction, Genetic
  • Transfection
  • Tumor Burden


  • Antigens, Neoplasm
  • Cytokines
  • GPI-Linked Proteins
  • Lysosomal-Associated Membrane Protein 1
  • Neoplasm Proteins
  • PSCA protein, human
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins