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Phase I Trial of a Modified Vaccinia Ankara Priming Vaccine Followed by a Fowlpox Virus Boosting Vaccine Modified to Express Brachyury and Costimulatory Molecules in Advanced Solid Tumors.


ABSTRACT: LESSONS LEARNED:Modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury followed by fowlpox virus-BN-Brachyury was well tolerated upon administration to patients with advanced cancer. Sixty-three percent of patients developed CD4+ and/or CD8+ T-cell responses to brachyury after vaccination. BN-Brachyury vaccine also induced T-cell responses against CEA and MUC1, which are cascade antigens, that is, antigens not encoded in the vaccines. BACKGROUND:Brachyury, a transcription factor, plays an integral role in the epithelial-mesenchymal transition, metastasis, and tumor resistance to chemotherapy. It is expressed in many tumor types, and rarely in normal tissues, making it an ideal immunologic target. Bavarian Nordic (BN)-Brachyury consists of vaccination with modified vaccinia Ankara (MVA) priming followed by fowlpox virus (FPV) boosting, each encoding transgenes for brachyury and costimulatory molecules. METHODS:Patients with metastatic solid tumors were treated with two monthly doses of MVA-brachyury s.c., 8 ×?108 infectious units (IU), followed by FPV-brachyury s.c., 1 ×?109 IU, for six monthly doses and then every 3 months for up to 2?years. The primary objective was to determine safety and tolerability. RESULTS:Eleven patients were enrolled from March 2018 to July 2018 (one patient was nonevaluable). No dose-limiting toxicities were observed. The most common treatment-related adverse event was grade 1/2 injection-site reaction observed in all patients. Best overall response was stable disease in six patients, and the 6-month progression-free survival rate was 50%. T cells against brachyury and cascade antigens CEA and MUC1 were detected in the majority of patients. CONCLUSION:BN-Brachyury vaccine is well tolerated and induces immune responses to brachyury and cascade antigens and demonstrates some evidence of clinical benefit.

SUBMITTER: Collins JM 

PROVIDER: S-EPMC7356719 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Phase I Trial of a Modified Vaccinia Ankara Priming Vaccine Followed by a Fowlpox Virus Boosting Vaccine Modified to Express Brachyury and Costimulatory Molecules in Advanced Solid Tumors.

Collins Julie M JM   Donahue Renee N RN   Tsai Yo-Ting YT   Manu Michell M   Palena Claudia C   Gatti-Mays Margaret E ME   Marté Jennifer L JL   Madan Ravi A RA   Karzai Fatima F   Heery Christopher R CR   Strauss Julius J   Abdul-Sater Houssein H   Cordes Lisa L   Schlom Jeffrey J   Gulley James L JL   Bilusic Marijo M  

The oncologist 20191226 7


<h4>Lessons learned</h4>Modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury followed by fowlpox virus-BN-Brachyury was well tolerated upon administration to patients with advanced cancer. Sixty-three percent of patients developed CD4+ and/or CD8+ T-cell responses to brachyury after vaccination. BN-Brachyury vaccine also induced T-cell responses against CEA and MUC1, which are cascade antigens, that is, antigens not encoded in the vaccines.<h4>Background</h4>Brachyury, a transcription fac  ...[more]

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