A phase I dose escalation trial of immunisation with autologous dendritic cells pulsed with NY-ESO-1 peptide and α-galactosylceramide in patients with high-risk surgically resected stage II, III or IV melanoma — ASN Events
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A phase I dose escalation trial of immunisation with autologous dendritic cells pulsed with NY-ESO-1 peptide and α-galactosylceramide in patients with high-risk surgically resected stage II, III or IV melanoma (#100)

Olivier Gasser 1 , Catherine Barrow 2 , Katrina Sharples 3 , Geoffrey Williams 4 , Evelyn Bauer 1 , Catherine Wood 1 , Brigitta Mester 1 , Marina Dzhelali 2 , Graham Caygill 5 , Jeremy Jones 5 , Colin Hayman 6 , Rob Weinkove 1 , Monica McClusker 7 , Sarah Benge 7 , Victoria Hinder 7 , Jerome Macapagal 7 , Gavin Painter 6 , Margaret Brimble 4 , Michael Findlay 7 , Rod Dunbar 4 , Ian Hermans 1
  1. Malaghan Institute of Medical Research, Wellington, New Zealand
  2. Capital and Coast District Health Board, Wellington, New Zealand
  3. University of Otago, Dunedin, New Zealand
  4. University of Auckland, Auckland, New Zealand
  5. Glycosyn, Wellington, New Zealand
  6. Ferrier Institute, Victoria University of Wellington, Wellington, New Zealand
  7. Cancer Trials New Zealand, University of Auckland, Auckland, New Zealand

Activation of NKT cells with α-galactosylceramide (α-GalCer) in the lymphoid tissues has been shown to provide an environment that is conducive to the development of T cell-mediated immune responses in animal models. Based on this pre-clinical evidence, we conducted a phase I trial of α-GalCer-adjuvanted vaccines in patients with high-risk surgically resected stage II, III or IV melanoma. The vaccines consisted of autologous monocyte-derived dendritic cells (DC) pulsed with α-GalCer together with synthetic long peptides derived from the cancer testis antigen NY-ESO-1 and a series of MHC class I-binding peptides derived from influenza virus proteins. The primary objective was to determine the dose of DC vaccine to be used in a phase II trial, now in progress, where responses to peptide-pulsed DC vaccines with and without α-GalCer will be compared. Eight patients were enrolled in the phase I trial; three patients received two cycles of vaccine administered intravenously one month apart at a dose of 1 x 106 DCs, two patients received one cycle at a dose of 3.4 x 106 DCs, and a further three patients received two cycles of 3.4 x 106 DCs. The immunotherapy was well tolerated, with no dose-limiting toxicity. Analysis of peripheral blood mononuclear cells and serum collected before and after treatment showed evidence of vaccine-induced NKT cell activation, and also stimulation of peptide-specific T cell responses that could be detected ex vivo without need for in vitro restimulation.