Author: Brendan Curti, M.D., medical director, Melanoma Program, and Cytokine and Adoptive Immunotherapy and Genitourinary Oncology Research, Providence Cancer Institute
For 70 years, the standard of care for men with metastatic prostate cancer has been medication or surgery to lower testosterone, also known as androgen deprivation therapy (ADT). In the last 10 years, a new class of medications that blocks the action of testosterone in prostate cancer cells has been commonly prescribed with ADT. Additionally, chemotherapy medications and targeted therapies are available.
How vaccine-based immunotherapy is different
Current treatments delay the growth of prostate cancer, frequently improve cancer-related symptoms and can extend longevity, but do not cure advanced disease. Immunotherapy using checkpoint antibodies such as nivolumab or pembrolizumab have improved outcomes in many cancers but not in prostate cancer. The main hypothesis for why checkpoint immunotherapies have not been successful is that prostate cells have fewer mutations compared to other cancers. Fewer mutations mean immune cells have fewer targets to pursue, and checkpoint therapy cannot overcome that.
Vaccine-based immunotherapy works differently compared to checkpoint therapy and holds promise in treating prostate cancer. The main idea behind cancer vaccines is to focus an immune response against proteins that distinguish the cancer from normal cells. There are several proteins in prostate cancer that can serve as vaccine targets, including PSA and PAP.
Virus triggers immune response
In this first-in-human phase I/II trial, Providence Cancer Institute clinical researchers are evaluating HB-302/HB-301 vaccine comprised of genetically engineered arenaviruses known as lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV). LCMV and PICV can cause significant illness in humans, but HB302-HB-301 are diminished so that viral infection and spread in normal tissues are minimized. The modified viruses also contain genes for PSA and PAP.
Normally, an immune response against PSA and PAP does not occur in men because both are normal self-proteins. The expectation for the vaccine is that the genetically modified viruses induce a strong immune response that starts in antigen-presenting cells (APCs). APCs are found in lymph nodes and other tissues, such as skin. Their main job is to ingest and process protein byproducts from normal cells or microbes (including viruses) and orchestrate immune responses to what is foreign in the body. The LCMV and PICV viruses cause a specific type of inflammation that strengthens immune reactions in APCs sufficient to break tolerance to self-proteins such as PAP and PSA.
The APCs do not directly kill cancer cells, but they can orchestrate a T-cell response (specifically effector cytotoxic T lymphocytes or CTLs). CTLs can move throughout the body and kill cancer cells. This vaccine mechanism has been demonstrated in pre-clinical models. In those models, the CTL response was enhanced by alternating LCMV and PICV vaccinations. This strategy of alternating viral vectors is sometimes called prime and boost vaccination. The clinical trial will use this prime and boost strategy to induce CTL responses against PSA and PAP.
Providence Cancer Institute Prostate Cancer Program
Providence Cancer Institute currently has six clinical trials for patients with advanced genitourinary cancers. “Clinical trials have led to incredible progress in cancer care and are essential for developing new treatments and for helping us take better care of our patients,” says Emily M. Lin, M.D., a medical oncologist with expertise in genitourinary cancers at Providence Cancer Institute Oncology and Hematology Care Clinic. Dr. Lin practices at Providence’s east- and west-side clinics. “They can be particularly helpful for patients for whom standard options are limited or aren't a good fit.”
Providence offers a range of treatments for patients with genitourinary cancers, including:
- Hormone therapy
Other treatments include surgical procedures to remove cancer from the body and MRI-guided radiation therapy via MRI Linac technology. Findings from a recent phase III trial published in JAMA Oncology showed that patients with localized prostate cancer who were treated with MRI-guided radiation had better outcomes. We also offer radiopharmaceutical treatments for selected patients with advanced prostate cancer.
Patients with locally advanced, recurrent or metastatic prostate cancer can be referred to one of our specialists at either location:
- Providence Cancer Institute Franz Clinic: Ref33x (OPH PCI FRANZ HEMA ONC)
- Providence Cancer Institute Westside Clinic: Ref33x (PROV ONCOLOGY AND HEMATOLOGY CARE)
To refer a patient to a clinical trial:
Dr. Curti also is member of the Earle A. Chiles Research Institute and the institute’s Robert W. Franz Endowed Chair for Clinical Research.
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