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Cancer Immunol Immunother. 2018 Feb;67(2):285-298. doi: 10.1007/s00262-017-2085-9. Epub 2017 Nov 1.

A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients.

Author information

1
Malaghan Institute of Medical Research, PO Box 7060, Wellington, 6242, New Zealand.
2
Dunedin School of Medicine, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
3
Cancer Trials New Zealand, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
4
Capital and Coast District Health Board, Private Bag 7902, Wellington, 6242, New Zealand.
5
Maurice Wilkins Centre for Molecular Biodiscovery, Private Bag 92019, Auckland, 1142, New Zealand.
6
GlycoSyn, PO Box 31 310, Lower Hutt, 5040, New Zealand.
7
The Ferrier Research Institute, Victoria University of Wellington, PO Box 33436, Lower Hutt, 5046, New Zealand.
8
School of Biological Sciences, University of Auckland, PO Box 92019, Auckland, New Zealand.
9
Malaghan Institute of Medical Research, PO Box 7060, Wellington, 6242, New Zealand. ihermans@malaghan.org.nz.
10
Maurice Wilkins Centre for Molecular Biodiscovery, Private Bag 92019, Auckland, 1142, New Zealand. ihermans@malaghan.org.nz.
11
School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington, 6140, New Zealand. ihermans@malaghan.org.nz.

Abstract

Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). In this phase I dose escalation study, we treated eight patients with high-risk surgically resected stage II-IV melanoma with intravenous autologous monocyte-derived DCs loaded with the NKT cell agonist α-GalCer and peptides derived from the cancer testis antigen NY-ESO-1. Two synthetic long peptides spanning defined immunogenic regions of the NY-ESO-1 sequence were used. This therapy proved to be safe and immunologically effective, inducing increases in circulating NY-ESO-1-specific T cells that could be detected directly ex vivo in seven out of eight patients. These responses were achieved using as few as 5 × 105 peptide-loaded cells per dose. Analysis after in vitro restimulation showed increases in polyfunctional CD4+ and CD8+ T cells that were capable of manufacturing two or more cytokines simultaneously. Evidence of NKT cell proliferation and/or NKT cell-associated cytokine secretion was seen in most patients. In light of these strong responses, the concept of including NKT cell agonists in vaccine design requires further investigation.

KEYWORDS:

Dendritic cell; Melanoma; NKT cell; NY-ESO-1; α-Galactosylceramide

PMID:
29094183
DOI:
10.1007/s00262-017-2085-9
[Indexed for MEDLINE]

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