Preliminary report of a novel formulation of clinical-grade, fully matured, tumor-associated peptide-loaded dendritic cells for cancer immunotherapy

Leonardo Mirandola,Francesco M Marincola,Jose A Figueroa,Robert Bresalier,Scott Dahlbeck,Maurizio Chiriva-Internati

doi:10.1186/s41231-019-0049-0

Leonardo Mirandola, Francesco M Marincola + Show 4 more

Open Access

https://doi.org/10.1186/s41231-019-0049-0

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Abstract

BackgroundWe developed and clinically test a new method to manufacture mature dendritic cells for autologous cell therapy of solid and hematological malignancies.MethodsPeripheral 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.ResultsHigh-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.ConclusionWe 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 registrationNCT02705703.

Highlights

We developed and clinically test a new method to manufacture mature dendritic cells for autologous cell therapy of solid and hematological malignancies
The majority of the clinical studies originated from prostate cancer and renal cell carcinoma, which showed that dendritic cells (DC) adoptive transfer elicited Tcell tumor responses in more than 50% of subjects [10]
Generation of immature DC To enrich the Peripheral blood mononuclear cell (PBMC) cultures in monocytes, after 2-h incubation at 37 °C and 5% CO2, non-adherent cells were removed from the flasks, and adherent cells were cultured in DC-medium supplemented with 800 U/mL GM-CSF and 1000 U/mL IL-4

Summary

Introduction

We developed and clinically test a new method to manufacture mature dendritic cells for autologous cell therapy of solid and hematological malignancies. The majority of the clinical studies originated from prostate cancer and renal cell carcinoma, which showed that DC adoptive transfer elicited Tcell tumor responses in more than 50% of subjects (and up to 70%) [10]. Despite their safety and demonstrated immunogenicity, DC therapies have shown poor objective clinical response [12].

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