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160 Recombinant Vector-Based Vaccines for Cancer Therapy

Schlom, Jeffrey Ph.D.

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 67
doi: 10.1097/01.qai.0000397346.84932.d3

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD

We have developed a recombinant viral vector-based vaccine platform consisting of a recombinant vaccinia (rV-) prime followed by multiple booster vaccinations with a recombinant fowlpox (rF-). Each vector contains the transgenes for one or more tumor-associated antigens, and transgenes for 3 human T-cell costimulatory molecules (designated TRICOM). A prostate cancer vaccine (PSA-TRICOM) has been designated PROSTVAC. Patients (n=125) with metastatic castrate-resistant prostate cancer were accrued in a 43-center, randomized placebo-controlled Phase II study. At 3 years post-study, PROSTVAC patients had a better overall survival with 30% alive vs. 17% of controls, and longer median survival by 8.5 months (25.1 vs. 16.6 months for controls; p=0.006).

A concurrent single-arm Phase II study with the same vaccine and similar patient population has also recently been completed with similar results. Regulatory T-cell suppressive function was shown to decrease following vaccine in patients surviving longer than predicted and increase in patients surviving less than predicted.

We envision these TRICOM vaccines as part of an immune-oncology platform. Several hypothesis-generating Phase II clinical studies in patients with breast and prostate cancer employing TRICOM vaccines in combination with radiation, hormone therapy or chemotherapy have recently been completed or are in progress with promising results. Several of these trials have now provided evidence for a paradigm shift in the design and evaluation of vaccine clinical trials either as monotherapy or in combination therapy.

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