This summary is from the 2015 Prostate Cancer Conference where in his lecture, Charles Drake, MD, discussed Immunotherapy. Dr. Drake is a pioneer in the advancement of immunotherapy. Here is the summary:
Biology of Immune Check Points
Single Agents have not worked so well in Prostate Cancer
Goal of Immunotherapy:
Get Killer T Cells into the cancer and kill the Tumor Cells.
Goal of cancer treatment/Immunotherapy treatment:
- Stop treatment after a period of time on therapy while sustaining a stable response
Killer T cells (aka: Death Whisperer):
- Killer T cells are Immune cells that kill normal cells that have been infected with virus.
- Killer T cells reach target cancer cells, punch holes in them causing them to explode.
- Cancer cells commit suicide when “told” to do so by Killer T cells.
- Killer T cells traffic throughout the body.
- They are also in prostates that are infected with prostate cancer.
Road Block for Killer T Cells:
- Immune Check Points
Immune Check Points:
- A series of molecules that put brakes on Killer T Cells.
- These molecules tell the Killer T Cells to mellow out (turn “off”).
Immune Check Points:
- PD1 Molecule
- CTLA-4 Molecule
Immune Check Point Blockade:
- Anti-PD1: (Nivolumab agent *1) monoclonal antibodies that block the integration between PD1 and PDL1 from interaction
- Anti CTLA-4: (Ipilimumab agent *2) lived one month longer
- As single agent “PD1 Blockade” did not resolve in any objective responses in prostate cancer… Immune Check Point blockade has not been a major hit in prostate cancer.
- AR-V7 - Biomarker: Variant of the androgen receptor predicts if patient is going to respond to Abiraterone or Enzalutamide (Blood test being done at John Hopkins)
- Combining Hormonal Therapy with Immunotherapy
- Combining Cancer Vaccine (Sepuleucel T) with Immunotherapy
- Dr. Julie Graff (Oregon). Men with MRPC who are progressing on Enzalutamide
- UCSF & MD Anderson. Vaccine & Immunotherapy
- FDA approved
- 2 Treatments over 4 weeks
- No PSA changes (like Prostvac)
- Tips balance in favor of patient vs Tumor. Survival stats
- Trial shows to use Provenge first (before hormone therapy)
- Can use Provenge with second phase hormone drugs
- Have treatment right after Provenge, do not wait until you see a PSA response
1. * Ipilimumab agent not approved
2. * Nivolumab agent approved for kidney cancer
- T-CELLS: Lymphocyte of a type produced by the thymus gland, actively participating in the immune response.
- Lymphocyte: Type of white blood cell
Charles Drake, MD is the Co-Director of Prostate Cancer Multi-Disciplinary Clinic, a Professor of Oncology at John Hopkins and an expert in immunotherapy and cancers of the prostate, kidney, bladder, and testes, Dr. Drake has published extensively and received numerous awards and honors for his research and scholarship, along with several patents. He is a member of the American Association of Immunology, the American Association of Cancer Research, and the American Society of Clinical Oncology.