Targeting Metastatic Prostate Cancer with Tumor-Specific Marrow-Infiltrating Lymphocytes (MILs)
Abstract
The overall goal of the proposed studies is to develop a new type of personalized immune-based therapy for men with advanced prostate cancer. With the amazing success stories of various immunotherapies over the past few years, it has become clear that the immune system frequently recognizes “mutated” (i.e., altered) proteins found on cancer cells, but unfortunately this recognition is not sufficient to prevent cancer progression in many cases due to escape mechanisms used by the tumor that block anti-tumor immune responses. The good news is the body stores “memory” of this tumor recognition on special immune cells that live in the bone marrow, known as memory T cells or marrow-infiltrating lymphocytes (MILs), which are normally maintained in a “resting” state. We can take advantage of this by isolating the tumor-specific memory T cells from the bone marrow and growing outside the body to “activate” them using very safe, quick, and specialized but relatively simple routine methods. Following expansion outside the body, these super-activated tumor-targeted cells can be re-infused back into the patient to hunt down and kill cancer cells spread throughout their body. Though this type of therapy has never been tried for prostate cancer, extremely promising results have been reported by our team when using them to treat multiple myeloma. Importantly, MILs have been successfully expanded from all patients in these studies and have shown remarkable anti-tumor responses with no safety concerns or signs of toxicity following treatment. Therefore, we plan to isolate MILs from prostate cancer patients and characterize their anti-tumor potential in preclinical assays and prostate cancer models. Not only will these studies provide important information regarding how the immune system interacts with prostate cancer cells that may lead to new biological understanding of the disease and even prognostic information to identify patients with “bad” disease, but will also provide the information needed to support further development of this therapy in men with high-risk or metastatic prostate cancer. Initial translation of the therapy into the clinic for testing in prostate cancer could happen very rapidly upon completion of the proposed studies. Potentially within just a few years based on our team’s prior experience and expertise in developing this approach for multiple myeloma, which is already beginning to make real improvements in patients with no other options.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710528
Entities
People
- Nathaniel Brennen
Organizations
- Johns Hopkins University
- United States Army