Erschienen in:
12.06.2017 | Original Article
Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer
verfasst von:
Guru Sonpavde, John D. McMannis, Yu Bai, Mamatha R. Seethammagari, Joan M. C. Bull, Victoria Hawkins, Theresa K. Dancsak, Natasha Lapteva, Jonathan M. Levitt, Annemarie Moseley, David M. Spencer, Kevin M. Slawin
Erschienen in:
Cancer Immunology, Immunotherapy
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Ausgabe 10/2017
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Abstract
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation. Eighteen men with progressive mCRPC following ≤1 prior chemotherapy regimen were enrolled to evaluate three doses of BPX101 (4 × 106, 12.5 × 106 and 25 × 106 cells) administered intradermally every 2–4 weeks followed by rimiducid (0.4 mg/kg) intravenous (IV) infusion 24 h after each BPX101 dose. There were no dose-limiting toxicities. Immune upregulation as well as anti-tumor activity was observed with PSA declines, objective tumor regressions and robust efficacy of post-trial therapy. This novel antigen-targeted and in vivo activated immunotherapy platform may warrant further development as monotherapy and as a component of rational combinations.