Cancer Immunology, Immunotherapy

, Volume 63, Issue 9, pp 959–967

Optimized dendritic cell-based immunotherapy for melanoma: the TriMix-formula

Authors

  • Sandra Van Lint
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
  • Sofie Wilgenhof
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
    • Department of Medical OncologyUniversity Hospital Brussel (UZ Brussel)
  • Carlo Heirman
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
  • Jurgen Corthals
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
  • Karine Breckpot
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
  • Aude Bonehill
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
  • Bart Neyns
    • Department of Medical OncologyUniversity Hospital Brussel (UZ Brussel)
    • Laboratory of Molecular and Cellular Therapy & Dendritic Cell-bankVrije Universiteit Brussel
    • Department of Medical OncologyUniversity Hospital Brussel (UZ Brussel)
Focussed Research Review

DOI: 10.1007/s00262-014-1558-3

Cite this article as:
Van Lint, S., Wilgenhof, S., Heirman, C. et al. Cancer Immunol Immunother (2014) 63: 959. doi:10.1007/s00262-014-1558-3

Abstract

Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. In this regard, one of the major focuses of cancer immunotherapy has been the design of vaccines promoting strong tumor-specific cytotoxic T lymphocyte responses in cancer patients. Here, dendritic cells (DCs) play a pivotal role as they are regarded as nature’s adjuvant and as such have become the natural agents for antigen delivery in order to finally elicit strong T cell responses (Villadangos and Schnorrer in Nat Rev Immunol 7:543–555, 2007; Melief in Immunity 29:372–383, 2008; Palucka and Banchereau in Nat Rev Cancer 12:265–277, 2012; Vacchelli et al. in Oncoimmunology 2:e25771, 2013; Galluzzi et al. in Oncoimmunology 1:1111–1134, 2012). Therefore, many investigators are actively pursuing the use of DCs as an efficient way of inducing anticancer immune responses. Nowadays, DCs can be generated at a large scale in closed systems, yielding sufficient numbers of cells for clinical application. In addition, with the identification of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, a whole range of strategies using DCs for immunotherapy have been designed and tested in clinical studies. Despite the evidence that DCs loaded with tumor-associated antigens can elicit immune responses in vivo, clinical responses remained disappointingly low. Therefore, optimization of the cellular product and route of administration was urgently needed. Here, we review the path we have followed in the development of TriMixDC-MEL, a potent DC-based cellular therapy, discussing its development as well as further modifications and applications.

Keywords

19th Danish Cancer Society Symposium 2013Dendritic cellmRNAImmunotherapyCancer

Abbreviations

API

Active pharmaceutical ingredient

caTLR4

Constitutive active form of Toll-like receptor 4

CD40L

CD40 ligand

CTLA-4

Cytotoxic T-Lymphocyte antigen 4

CTLs

Cytotoxic T lymphocytes

DCs

Dendritic cells

DTH

Delayed-type hypersensitivity

GM-CSF

Granulocyte/macrophage colony-stimulating factor

GMP

Good manufacturing practice

HBSS

Hanks balanced salt solution

HLA

Human leukocyte antigen

i.d.

Intradermal

i.n.

Intranodal

i.v.

Intravenous

mAbs

Monoclonal antibodies

MP

Medicinal product

NGS

Next-generation sequencing

SKILs

Skin-infiltrating lymphocytes

TH1

T helper 1

TLR

Toll-like receptor

Treg

Regulatory T cell

TriMixDC-MEL

TriMixDCs co-electroporated with mRNA encoding a fusion of DC-LAMP and one of four melanoma-associated antigens: gp100, tyrosinase, MAGE-A3 and MAGE-C2

Copyright information

© Springer-Verlag Berlin Heidelberg 2014