The PCF Challenge Award Winners – Class of 2019 recipients are:
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)
Project Title: L1CAM Chimeric Antigen Receptor T Cell Therapy for Small Cell Neuroendocrine Prostate Cancer
- 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.
Principal Investigator: Eliezer Van Allen, MD (Harvard: Dana Farber Cancer Institute), Nikolaus Schultz, PhD (Memorial Sloan Kettering Cancer Center), Wassim Abida, MD, PhD (Memorial Sloan Kettering Cancer Center), Deborah Schrag, MD, MPH (Harvard: Dana Farber Cancer Institute)
Co-Investigators: Haitham Elmarakeby, PhD (Harvard: Dana Farber Cancer Institute)
Project Title: A Genomics-Guided Clinical Interpretation and Translational Discovery Engine for Prostate Cancer
- Prostate cancer is a highly variable disease, which differs across and even within patients. Understanding the biological and clinical variations and how best to treat individual patients is of great need. The ability to harness and learn from the vast amounts of existing multi-dimensional patient data will enable researchers and clinicians to identify and apply optimal precision medicine treatment strategies for all patients.
- Eliezer Van Allen and team will develop a prostate cancer patient registry that will capture clinical data (which includes treatments and outcomes), pathology and imaging data, and data on tumor mutations, from over 10,000 patients spanning all stages of disease.
- The team will develop artificial intelligence algorithms to identify clinical and/or molecular features that predict patient outcomes and responses to treatments. Relationships that are identified between genomic alterations and prostate cancer outcomes will be studied and validated in experimental models.
- A significant amount of clinical information is included in medical reports in a non-standardized fashion. The team will develop biomedical natural language models that can extract information from medical reports including disease classification, regression, and survival prediction. The team will also build algorithms to read radiographic images and convert this information into standardized data.
- All of these data will be combined with other patient clinical and molecular data in the registry and used to create a single model that can predict patient outcomes and treatment responses.
- The team will also develop a digital clinical trials framework and an algorithm that will enable clinicians to match patients to precision medicine clinical trials based on their clinical, genomic, and other features.
- If successful, this project will develop a rich data resource for the research and clinical community, as well as algorithms to learn from this data and to apply it directly toward making immediate optimal precision medicine treatment decisions for patients with prostate cancer.
What this means to patients: Precision medicine is an emergent clinical approach in which patients’ treatment plans are made based on their unique personal and tumor features. Dr. Van Allen and team will develop a prostate cancer registry that contains multi-dimensional patient data, and create algorithms that can predict patient outcomes. The team will also build a digital resource to match patients with optimal precision medicine clinical trials. This project will significantly accelerate precision medicine for all men with prostate cancer.
Principal Investigator: Charles Drake, MD, PhD (Columbia University; NewYork-Presbyterian)
Co-Investigators: Raul Rabadan, PhD (Columbia University), Matthew Dallos, MD (Columbia University; NewYork-Presbyterian)
Project Title: Maximizing Androgen Deprivation ImmunoGenICity through PD-1 and IL-8 Blockade in Lethal Prostate Cancer (MAGIC-8)
- Immunotherapy is a promising type of cancer therapy that activates a patient’s own immune system to fight their cancer. Immunotherapy has been highly effective in some cancers such as melanoma and lung cancer, but has yet to be optimized for prostate cancer.
- Charles Drake and team are developing a new immunotherapy treatment regimen that can effectively activate anti-tumor immune responses in prostate cancer.
- The team previously discovered that prostate tumors secrete an immune suppressive protein, IL-8, especially during treatment with androgen deprivation therapy (ADT).
- Based on these findings, the team is conducting a clinical trial (MAGIC-8) which combines a novel IL-8-targeting treatment, with the immune activating therapy nivolumab, and ADT, in men with hormone-sensitive recurrent prostate cancer.
- In this project, the team will use samples from the patients on this trial to investigate key biological changes needed to re-establish anti-tumor immunity in prostate cancer and identify biomarkers that can predict treatment responses.
- The team will determine the impact of this immunotherapy combination treatment regimen on the types and numbers of immune cells infiltrating the tumor, including whether the treatment alters the balance between tumor-killing and tumor-promoting immune cell types.
- How this immunotherapy regimen affect the total body (systemic) immune system state will be investigated.
- Whether specific tumor mutations or expression of master cancer-driving proteins are associated with clinical responses to treatment with IL-8-blockade and nivolumab will be investigated.
- If successful. This project will result in the development of a new immunotherapy regimen that will extend the lives of patients, as well as uncover biology and biomarkers of treatment responses.
What this means to patients: New strategies are needed in order to harness the power of the immune system as an effective therapeutic in men with prostate cancer. Dr. Drake and team are conducting a clinical trial testing a novel immunotherapy regimen that combines a drug that blocks immune suppression with a drug that enhances anti-cancer immune activity. This project will determine the clinical and biological effects of this treatment in patients, and develop biomarkers that can predict which patients are most likely to respond.