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Poster Display session

477 - Impact of different GMP media in the production of dendritic cells for next-generation cancer immunotherapy: Functional and metabolic characterization

Date

14 Dec 2018

Session

Poster Display session

Presenters

João Calmeiro

Citation

Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485

Authors

J. Calmeiro1, M. Carrascal2, C. Gomes3, A. Falcão4, J. Serra2, M.T. Cruz1, B. Neves5

Author affiliations

  • 1 Faculty Of Pharmacy, University of Coimbra, 3004-548 - Coimbra/PT
  • 2 Tecnimede Sa, Grupo Tecnimede, 2710-089 - Sintra/PT
  • 3 Coimbra Institute For Clinical And Biomedical Research, Faculty Of Medicine, University of Coimbra, 3000-354 - Coimbra/PT
  • 4 Coimbra Institute For Biomedical Imaging And Translational Research (cibit), University of Coimbra, 000-548 - Coimbra/PT
  • 5 Department Of Medical Sciences And Institute Of Biomedicine – Ibimed, University of Aveiro, 3810-193 - Aveiro/PT
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Resources

Abstract 477

Background

Dendritic cells (DCs) are unique antigen presenting cells that are used in cancer immunotherapy, with more than 20 years of clinical trials in this field. The production of clinical grade monocyte-derived DCs is highly desired and globally performed, with a large space for improvement and development of clinical standard operating procedures (CSOP). This process is highly dependent on three constraints: used cytokines for cell differentiation, maturating agents and culture medium. There is a clear lack of studies focusing on how the used culture medium and its composition and components affect the process of ex-vivo generation of monocyte-derived DCs. This study aims to compare the effect of 4 culture media (3 GMP media and 1 medium widely used in research) during monocyte-derived DCs differentiation.

Methods

We characterized DC viability, differentiation, maturation, internalization of tumor lysates, cytokines production and autologous T cell stimulatory capacity, as well as metabolomic profiles. Commercially available culture media for clinical use were tested, namely DendriMACS, AIM-V and X-VIVO 15. RPMI was also tested as a comparative term given that it is largely used in pre-clinical research.

Results

In terms of differentiation, maturation, DC uptake capacity, and metabolic profiles, AIM-V and X-VIVO 15 present similar results. However, the use of X-VIVO 15 shows an enhanced DC production of IL-12. DCs cultured in X-VIVO 15 and AIM-V media are able to induce a superior stimulation of T cells, mainly CTLs and Th1 responses, while DCs cultured in DendriMACS are more prone to induce Treg polarization.

Conclusions

Our data show that X-VIVO 15 and AIM-V culture media are preferable to support the differentiation of DC to be used in immunostimulatory approaches such as in cancer cell therapy. Overall, this study highlights the need of previously and carefully defining the culture medium to be used in DC cancer immunotherapy, for a better aim to the therapeutic goal and potentiating the clinical experiment and final patient output.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Grupo Tecnimede.

Funding

This study received funding from the project ImmunoDCs@CancerStemCells: Cellular Immunotherapy towards the elimination of cancer stem cells (Ref.: POCI-01-0247-FEDER-033532), co-funded by the European Regional Development Fund (FEDER), Competitiveness and Internationalization Operational Program (COMPETE2020) and Own Revenues of the University of Coimbra. João Calmeiro is supported by the Portuguese Science and Technology Foundation (FCT) through an individual PhD fellowship (PD/BDE/135076/2017).

Disclosure

All authors have declared no conflicts of interest.

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