Cancer Vaccine

In a development likely to be viewed as a major milestone in the history of cancer therapy, the Food and Drug Administration on April 29, 2010 approved the first cancer vaccine, Provenge, developed by Dendreon Corp. for the treatment of advanced prostate cancer. In clinical trials, it extended the lives of patients about four months compared with placebo, longer than the 2 to 3 month survival advantage gained using the only other approved therapy for these patients, docetaxel chemotherapy, but without the serious side effects including fatigue, hair loss and neuropathy associated with chemotherapy. One unusual aspect of treatment with Provenge that has generated controversy is that the vaccine doesn’t shrink tumors or change the PSA level in most patients, so while the vaccine extends survival, patients have no way of knowing whether the vaccine is working.

Now, researchers at the Vanguard Urologic Institute at Memorial Hermann-Texas Medical Center are conducting a trial to test an innovative vaccine product, BPX-101, that builds on this success but will hopefully lead to more effective, longer responses in patients while maintaining the safety and lack of side effects seen with Provenge.

BPX-101 is a novel cancer vaccine specifically designed to be “activated” precisely at the optimal time and location in the body through the administration of an activating agent called AP1903. AP1903 acts as a molecular “key” that exactly fits a complementary molecular “switch” engineered into the cells comprising the vaccine product. AP1903 is administered to patients once vaccinated cells have traveled to local lymph nodes, where activation leads to a potent immune response against the targeted cancer cells. BPX-101 is designed to be effective against a broad range of cancers, including prostate cancer.

Developed by Kevin Slawin, M.D., a nationally recognized expert in prostate disease and director of the Vanguard Urologic Institute, in collaboration with Baylor College of Medicine researcher David Spencer, Ph.D., the promising new therapy is mid-way through completion of the first-in-human Phase I-II clinical trial for patients with mCRPC, with the results recently reported in a Late-Breaking abstract session at the 101st Annual Meeting of the American Association of Cancer Research held recently in Washington, D.C.

The trial was designed to establish the safety and maximum tolerated dose of BPX-101 in combination with activating agent AP1903, administered every other week for six doses. Exploratory efficacy endpoints include radiological and biochemical assessments of clinical response, and assessments of serum and biopsy samples for systemic and antigen-specific immunological responses.

Interim data from six subjects shows the combination of BPX-101, with no unexpected drug-related adverse events reported. Clinical responses, including shrinking tumors and reduced PSA levels, were evident within the first 12 weeks of treatment, in both low and mid dose cohorts.

The apparent dose-response correlation between clinical and immunological responses will be further investigated in six subjects now enrolling in the final, high dose cohort. “We are very excited and encouraged by this early data, which appears to contradict the prevailing belief that while cancer vaccines can prolong overall survival, they do not elicit measurable clinical or biomarker responses in the near term,” said Dr. Slawin. “We look forward to completing our trial later this year and initiating Phase II trials in 2011.”

All procedures are being conducted on an outpatient basis at the Memorial Hermann-TMC Clinical Research Unit under the auspices of The University of Texas Center for Clinical and Translational Sciences.

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