Author:
Mirandola Leonardo,Chiriva-Internati Maurizio,Bresalier Robert,Marincola Francesco M.,Figueroa Jose A.,Dahlbeck Scott
Abstract
Abstract
Background
We developed and clinically test a new method to manufacture mature dendritic cells for autologous cell therapy of solid and hematological malignancies.
Methods
Peripheral blood monocytes are matured into dendritic cells with GM-CSF/IL-4 mixture, and then activated through IL1b, TNFa, IFNa-2A, and Poly(I:C), then viably frozen until use. DC are injected intra-dermally for a total of 6 injections.
Results
High-grade mDC with high pre- and post- freezing yields could be generated. These DC spontaneously produce IL12p70 and they can be further stimulated via CD40. In a patient with advanced pancreatic cancer treated with our mDC formulation, we observed no toxicity but remarkable immune response and objective response in terms of tumor shrinking.
Conclusion
We describe a new method to manufacture GMP-grade dendritic cells for autologous therapeutic cancer vaccines. We also show proof-of-principle efficacy in a patient with advanced pancreatic cancer.
Trial registration
NCT02705703.
Publisher
Springer Science and Business Media LLC
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