Seminars in Immunopathology

, Volume 33, Issue 4, pp 369–383

Immunomodulatory effects of cyclophosphamide and implementations for vaccine design

Authors

  • Antonella Sistigu
    • INSERM, U1015
    • Institut Gustave Roussy
    • Université Paris-Sud
    • Department of Cell Biology and NeurosciencesIstituto Superiore di Sanità
  • Sophie Viaud
    • INSERM, U1015
    • Institut Gustave Roussy
  • Nathalie Chaput
    • INSERM, U1015
    • Institut Gustave Roussy
    • Centre d’Investigation Clinique en Biothérapie, CICBT 507
    • Laboratoire de Thérapie cellulaireInstitut Gustave Roussy
  • Laura Bracci
    • Department of Cell Biology and NeurosciencesIstituto Superiore di Sanità
  • Enrico Proietti
    • Department of Cell Biology and NeurosciencesIstituto Superiore di Sanità
    • INSERM, U1015
    • Institut Gustave Roussy
    • Université Paris-Sud
    • Centre d’Investigation Clinique en Biothérapie, CICBT 507
    • U1015 INSERMInstitut Gustave Roussy
Review

DOI: 10.1007/s00281-011-0245-0

Cite this article as:
Sistigu, A., Viaud, S., Chaput, N. et al. Semin Immunopathol (2011) 33: 369. doi:10.1007/s00281-011-0245-0

Abstract

Drug repositioning refers to the utilization of a known compound in a novel indication underscoring a new mode of action that predicts innovative therapeutic options. Since 1959, alkylating agents, such as the lead compound cyclophosphamide (CTX), have always been conceived, at high dosages, as potent cytotoxic and lymphoablative drugs, indispensable for dose intensity and immunosuppressive regimen in the oncological and internal medicine armamentarium. However, more recent work highlighted the immunostimulatory and/or antiangiogenic effects of low dosing CTX (also called “metronomic CTX”) opening up novel indications in the field of cancer immunotherapy. CTX markedly influences dendritic cell homeostasis and promotes IFN type I secretion, contributing to the induction of antitumor cytotoxic T lymphocytes and/or the proliferation of adoptively transferred T cells, to the polarization of CD4+ T cells into TH1 and/or TH17 lymphocytes eventually affecting the Treg/Teffector ratio in favor of tumor regression. Moreover, CTX has intrinsic “pro-immunogenic” activities on tumor cells, inducing the hallmarks of immunogenic cell death on a variety of tumor types. Fifty years after its Food and Drug Administration approval, CTX remains a safe and affordable compound endowed with multifaceted properties and plethora of clinical indications. Here we review its immunomodulatory effects and advocate why low dosing CTX could be successfully combined to new-generation cancer vaccines.

Keywords

CyclophosphamideChemotherapyImmunotherapyCancer vaccineImmunomodulationCancer

Copyright information

© Springer-Verlag 2011