Comparison of Clinical and Immunological Effects of Intravenous and Intradermal Administration of alpha-GalactosylCeramide (KRN7000)-Pulsed Dendritic Cells

Nicol, Andrew J., Tazbirkova, Andrea and Nieda, Mie (2011) Comparison of Clinical and Immunological Effects of Intravenous and Intradermal Administration of alpha-GalactosylCeramide (KRN7000)-Pulsed Dendritic Cells. Clinical Cancer Research, 17 15: 5140-5151. doi:10.1158/1078-0432.CCR-10-3105


Author Nicol, Andrew J.
Tazbirkova, Andrea
Nieda, Mie
Title Comparison of Clinical and Immunological Effects of Intravenous and Intradermal Administration of alpha-GalactosylCeramide (KRN7000)-Pulsed Dendritic Cells
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
Publication date 2011-08-01
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-10-3105
Open Access Status Not yet assessed
Volume 17
Issue 15
Start page 5140
End page 5151
Total pages 12
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Language eng
Abstract Human Vα24+Vβ11+ natural killer T-cells (NKT cells) have antitumor activity via direct cytotoxicity and by induction of antitumor actions of T and NK cells. Activation of NKT cells is crucial for their antitumor activity and is induced by α-galactosylceramide (α-GalCer, KRN7000) presented by CD1d on dendritic cells (DC). We conducted a phase I clinical trial of therapy with α-GalCer-pulsed DC to determine safety, tolerability, immune effects and an optimal dose, and administration route.

Twelve subjects (3 cohorts) with metastatic malignancy received 4 treatments of α-GalCer-pulsed DC, 2 treatments intravenously (IV), and 2 treatments intradermally (ID). Each successive cohort received a log higher cell dose. Clinical and immunological outcomes were evaluated, including secondary effects on NK and T cells.

Substantial effects on peripheral blood NKT cells were observed but were greater following IV treatment. Secondary immune effects including activation of T and NK cells, increases in T- and NK-cell cytoplasmic interferon-γ, and increases in serum interferon-γ levels were seen after IV but not after ID treatment. Therapy was well tolerated, but 9 of 12 subjects had tumor flares with clinical findings consistent with transient tumor inflammation. Disease response (minor) or stabilization of disease progressing up to enrollment was observed in 6 of the 12 subjects. Stabilization of previously progressive disease lasted for at least one year in three subjects.

We conclude that therapy with α-GalCer-pulsed DC induced clinically beneficial immune responses that are highly dependent on cell dose and administration route.
Keyword Killer T-Cells
V-Alpha-24 Nkt Cells
Phase-I
Cancer-Patients
Lung-Cancer
Tumor-Cells
Antitumor-Activity
Innate Nkt
Ifn-Gamma
Antigen
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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