Enhancing Antigen Presentation and Antitumor Immunity for Prostate Cancers Through an Intratumorally Delivered, Fc-Enhanced Anti-CD40 Antibody Therapy

Principal Investigators: Howard Scher, MD (Memorial Sloan Kettering Cancer Center), Behfar Ehdaie, MD, MPH (Memorial Sloan Kettering Cancer Center), David Knorr, MD, PhD (Memorial Sloan Kettering Cancer Center), Matthew Dallos, MD (Memorial Sloan Kettering Cancer Center)

Co-Investigators: Andrea Are, PhD (Memorial Sloan Kettering Cancer Center), Anuradha Gopalan, MD (Memorial Sloan Kettering Cancer Center), Christopher Gaffney, MD (Memorial Sloan Kettering Cancer Center)

Description:

• Immunotherapy has revolutionized the treatment of many cancers, but unfortunately has helped only a minority of patients with prostate cancer. It is therefore critical that new immunotherapy approaches are developed that can eliminate prostate cancer cells early in the course of a patient’s illness, prevent progression and recurrence and increase the potential for cure.
• Needed is a more in-depth understanding of how the immune system responds to the disease itself, and how it is affected by the androgen deprivation approaches that are the backbone of treatment for prostate cancer.
• The immune system identifies cells using a process that begins with antigen presentation. Howard Scher and team have found that the lack of effective antigen presentation is a critical bottleneck to the immune system’s ability to identify and attack the disease.
• CD40 is a protein found on the surface of immune cells. The team has found that targeting CD40, using a novel antibody vaccine developed by the team, can enhance the ability of the immune cells to kill the cancer cells both at the site of injection and in other sites of spread in patients with metastatic disease.
• Building on the collective efforts of this multidisciplinary team, this project will test this novel drug, known as a CD40 agonist, within the context of a clinical trial that includes patients with intermediate risk disease who can safely in the view of their treating physician, postpone radical prostatectomy to receive the drug alone, and separately, patients with high-risk localized or metastatic disease in combination with standard androgen deprivation therapy.
• These studies will significantly impact our understanding of the how and why prostate cancers remain resistant to immune-based approaches, as well as test a novel approach to overcoming barriers to achieving an effective immune response.
• If this treatment is effective, it may result in the elimination of all disease and enable patients with prostate cancer to live longer with an improved quality of life.

What this means to patients:  Immunotherapy is a highly promising form of cancer treatment, yet barriers remain to realizing the full potential these treatments for prostate cancer.  Dr. Scher and team have developed a novel immunotherapy that targets a key immune activation pathway and will test and determine the mechanisms of action of this treatment in patients with prostate cancer.  This may lead to an effective new, and possibly even curative treatment for prostate cancer.