Novel Immunotherapy for High-Risk Prostate Cancer Shows Preliminary Promise

In the past 20 years, a stage shift has occurred in prostate cancer presentation patterns. While aggressive screening programs can lead to early diagnosis and effective treatment, approximately 5 percent of men with prostate cancer present with advanced forms of malignancy. Moreover, as many as 50 percent of advanced cases considered to be localized may, in fact, have grown beyond the prostatic capsule, but the metastatic disease is not clinically detectable.

When this extracapsular growth occurs, patients are understaged at diagnosis and at risk for undertreatment. They can avoid this suboptimal scenario by seeking care at an advanced, comprehensive prostate center that provides the full spectrum of clinical, surgical, and emerging interventions, including promising immunotherapeutic strategies and clinical trials.

Scan showing prostate cancer

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Novel strategy

The rise of novel immunotherapies — primarily androgen-deprivation therapy (ADT) — is important because neither the treatment nor the prognosis of locally advanced high-risk prostate cases has changed greatly over the past 60 years. Although ADT provides palliative care, it is not a cure. Typically patients with prostate cancer have a disseminated tumor that becomes refractory to hormone therapy, placing the patient at considerable risk for swift progression and death.

In a study nearing completion,* Mayo Clinic urologists used a novel two-step therapeutic strategy to boost and harness the immune response to fight advanced prostate cancer.

1. Immunostimulation by ADT. Deprived of hormonal support through ADT, some tumor cells die and the tumor mass shrinks. These processes signal infiltration of activated immune cells.
2. Deployment of a monoclonal antibody molecule, MDX-010. After infiltrating the tumor, immune cells are manipulated with MDX-010 to help fight cancer. Synthesized in the laboratory, MDX-010 binds to the natural molecule CTLA-4 found on the surface of the immune system's T cells. By binding there, MDX-010 blocks the switch to the immune system in the on position, so it remains robustly active in attacking cancer cells.

Preliminary results

Two Mayo Clinic patients have responded unusually well to this strategy since 2007. In one patient, a single intravenous treatment rendered the cancer undetectable by scans and physical palpation. Before treatment, both imaging and physical examination results clearly documented extensive disease. During resection, pathology reports confirmed that 80 percent of the mass was gone. The patient recovered, was rendered off therapy, and remains disease free.

In 2008, a similar hype-rresponse occurred. Before treatment, the tumor measured approximately 50 cm3. After treatment, the tumor was undetectable — prompting the pathologist to telephone the surgical team during surgery to double check the identity of the patient. Pathologic examination documented extensive disaggregation of the tumor. The patient had complete downstaging of the disease, was taken off therapy, and remains disease free.

Downstaging disease

Although these two unusually strong responses comprise a small sample, they suggest possibilities that may lead to a pharmacologic means of downstaging disease or to a cure. Two possibilities are being studied:

• A phenotype may exist for a hyper-responder. If a phenotype can be identified, perhaps a means can be devised for conditioning patients to become hyper-responders.
• Prostate cancers may be hormone regulated. Many blood vessels are sensitive to hormones, but it is unknown whether this sensitivity is the mechanism at work in these unusual cases of downgraded diagnosis.

Enrolling patients

Research on this novel immunotherapeutic approach is ongoing at Mayo Clinic in Minnesota. Two new studies will be opening between late fall 2009 and early spring 2010:

• A study for patients who have locally advanced prostate cancer that has not been treated with hormones
• A study for patients with widely metastatic prostate cancer who have failed both hormone therapy and chemotherapy.

To inquire about enrolling patients in these studies, please phone 507-284-3369 or email MDX010@mayo.edu.

* Research supported by the Department of Defense, the Richard M. Schulze Family Foundation, Mayo Clinic Comprehensive Cancer Center, and Mayo Clinic Center for Translational Science Activities. Medarex, Inc. provided the free study drug. Mayo Clinic and the lead investigator have received royalties from Medarex from the licensing of technologies unrelated to this research.