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


Authors: Karbach, J.; Neumann, A.; Brand, K.; Wahle, C.; Siegel, E.; Maeurer, M.; Ritter, E.; Tsuji, T.; Gnjatic, S.; Old, L. J.; Ritter, G.; Jager, E.
Article Title: Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: Immunological effects and clinical activity
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 maybe 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. ©2012 AACR.
Keywords: clinical article; treatment response; unclassified drug; human cell; drug safety; side effect; cancer staging; outcome assessment; antigen expression; c reactive protein; protein blood level; interleukin 2; cancer immunotherapy; melanoma; interleukin 10; interleukin 13; interleukin 1beta; interleukin 5; interleukin 8; in vitro study; bladder cancer; enzyme linked immunosorbent assay; immunoregulation; drug dose escalation; drug fever; injection site reaction; prostate cancer; sarcoma; cancer regression; cellular immunity; immune response; tumor necrosis factor alpha; gamma interferon; cancer vaccine; antigen specificity; head and neck cancer; ny eso 1 antigen; interleukin 6; malignant neoplastic disease; injection site pain; open study; immunomodulation; flu like syndrome; weakness; immunostimulation; phase 1 clinical trial; humoral immunity; interleukin 12; concentration response; peripheral blood mononuclear cell; sweating; injection site pruritus; injection site swelling; body temperature; multiple drug dose; good manufacturing practice; mixed bacterial vaccine; injection site reddening
Journal Title: Clinical Cancer Research
Volume: 18
Issue: 19
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2012-10-01
Start Page: 5449
End Page: 5459
Language: English
DOI: 10.1158/1078-0432.ccr-12-1116
PROVIDER: scopus
PUBMED: 22847809
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sacha Gnjatic
    111 Gnjatic
  2. Gerd Ritter
    156 Ritter
  3. Erika Ritter
    34 Ritter
  4. Takemasa Tsuji
    14 Tsuji
  5. Lloyd J Old
    381 Old