IMMUNOTHERAPY IN HEAD & NECK SQUAMOUS CELL CARCINOMA

THE GOAL OF CANCER IMMUNOTHERAPY

It is now known that defects in the dendritic cells (DCs) and helper and cytotoxic T cells exist in cancer and that these must be corrected for effective cellular immune responses. In addition, tumors induce immune suppression through multiple mechanisms. Thus, next generation active immunotherapies must also effectively counteract tumor-induced immune suppression. The targets for active immunotherapy include:

  • Restoring immunization by
    • Correcting the DC maturation defect
    • Correcting the T-cell activation defect
  • Counteracting tumor-induced immune suppression by
    • Inhibiting T regulatory cells
    • Protecting against tumor exosomes (microvesicles bearing tumor antigen and FAS ligand)
    • Reducing soluble factor production by tumors, including: VEGF, TGF−β, PGE-2, and IL-10
IL, interleukin; PGE, prostaglandin E; TGF−β, transforming growth factor beta; VEGF, vascular endothelial growth factor.

THE NEED FOR MULTIPLE MECHANISMS OF ACTION IN CANCER IMMUNOTHERAPY

The current scientific view is that the immune system is capable of recognizing cancer cells as foreign and responding against them, but it does not do this because the immune system is suppressed by the cancer through multiple protective mechanisms. Given the numerous cellular defects present in cancer, however, it is unlikely that a single agent or cytokine will restore cellular immune responses. Additionally:

  • The immune system uses many cytokines to help coordinate its activities. Therefore, a biologic with multiple active components, rather than a single cytokine, may offer the possibility of greater benefit, as well as synergy among its components
  • Combination therapy could enable different mechanisms to be enlisted to restore cellular function and attack the tumor-induced immune suppression

IRX-2 MECHANISMS OF ACTION

The INSPIRE study is intended to provide evidence that IRX-2 activates and stimulates multiple components of the cellular immune system resulting in host recognition of disease, rejection, and immunization.

© 2016 IRX Therapeutics