Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: Immunological effects and clinical activity.

Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jäger E.
Journal   Clin Cancer Res.
Species  
Analytes Measured   GM-CSF , IL-10 , IL-12 Total , IL-2 , IL-4 , IL-5 , IL-6 , IL-8
Matrix Tested   Serum
Year   2012
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
PURPOSE: Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice-compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers.

EXPERIMENTAL DESIGN: Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST.

RESULTS: Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-β. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines.

CONCLUSIONS: MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines.

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Multiplex
V-PLEX Viral Panel 2 NHP Kit
IFN-γ, IL-1β, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Viral Panel 3 Human Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α | Human
Multiplex
V-PLEX Viral Panel 3 NHP Kit
IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
U-PLEX Human GM-CSF Assay
GM-CSF | Human
Singleplex
U-PLEX Human IL-2 Assay
IL-2 | Human
Singleplex
U-PLEX Human IL-4 Assay
IL-4 | Human
Singleplex
U-PLEX Human IL-5 Assay
IL-5 | Human
Singleplex
U-PLEX Human IL-6 Assay
IL-6 | Human
Singleplex
U-PLEX Human IL-8 Assay
IL-8 | Human
Singleplex
U-PLEX Human IL-10 Assay
IL-10 | Human
Singleplex
U-PLEX Mouse GM-CSF Assay
GM-CSF | Mouse
Singleplex
U-PLEX Mouse IL-2 Assay
IL-2 | Mouse
Singleplex
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