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2019 Movember-PCF Challenge Award

L1CAM Chimeric Antigen Receptor T Cell Therapy for Small Cell Neuroendocrine Prostate Cancer

Principal Investigators: John Lee, MD, PhD (Fred Hutchinson Cancer Research Center), Peter Nelson, MD (Fred Hutchinson Cancer Research Center)

Co-Investigators: Vicky Qian Wu, PhD (Fred Hutchinson Cancer Research Center), Navin Pinto, MD (Seattle Children’s Research Institute), Julie Park, MD (Seattle Children’s Research Institute), Diana DeLucia, PhD (Fred Hutchinson Cancer Research Center), Michael Jensen, MD (Seattle Children’s Research Institute)

Description:

  • Small cell neuroendocrine prostate cancer (SCNPC) is a highly aggressive and incurable form of advanced, therapy-resistant prostate cancer. The development of new treatments that are effective against SCNPC is an urgent unmet medical need.
  • Dr. John Lee and team are developing a novel CAR-T cell immunotherapy able to target and kill SCNPC cells.
  • CAR T cells are genetically engineered immune cells, that are made by uploading a patient’s own T cells with a gene that enables them to target and kill cells expressing a specific target protein.
  • Dr. Lee and team previously found that L1CAM may represent an ideal CAR T cell target in SCNPC, neuroblastoma, and other cancers. The team has already developed a L1CAM-targeting CAR T cell and have initiated a clinical trial testing this CAR T cell in patients with neuroblastoma.
  • In this project, the team will evaluate the potential efficacy of L1CAM-CAR T cells in preclinical prostate cancer models.
  • The team will also perform studies to improve the safety, efficacy and persistence of L1CAM-targeting CAR T cells, in order to develop a treatment that will be most effective in prostate cancer. Strategies to improve CAR T cells, such as adding in additional genetically engineered proteins to enable the T cells to resist immune suppression or have improved tumor-specific targeting and better safety, will be tested.
  • Finally, the team will initiate a phase 1 clinical trial testing the most promising L1CAM CAR T cell version in men with advanced SCNPC.
  • If successful, this project will develop a promising new immunotherapy that is effective in men with one of the worst forms of prostate cancer.

What this means to patients: Small cell neuroendocrine prostate cancer (SCNPC) is an aggressive and incurable form of prostate cancer for which effective treatments are urgently needed. Dr. Lee and team will develop a novel CAR T cell immunotherapy against SCNPC that will engineer a patients’ own immune cells to target and kill their cancer, and will test the safety and efficacy of this treatment in clinical trials.