IMMUNE DYSFUNCTION AND IMMUNOTHERAPY IN SCCHN

Patients with SCCHN are consistently found to have disordered immune function at the time of presentation. Although they have normal B-cell function, immunoglobulin levels, and complement systems, SCCHN patients have immunological deficiencies of T-cell anergy and defective monocyte/macrophage function.1,2 Human SCCHN tissues commonly expressed PD-L1, which downregulates T-cell mediated immunity.3

The cumulative result of the various immune defects and immunosuppressive mechanisms in SCCHN is1,2,4:

  • The tumor successfully subverts the antigen presentation component (ie, dendritic cell [DCs]) and the responding T-cell component of immunization, even though the tumor displays and sheds antigens capable of inducing an antitumor immune response
  • The compromised cellular immune response is, therefore, incapable of attacking and rejecting the tumor

STRATEGIES FOR TUMOR IMMUNOTHERAPY

Because tumors induce immune suppression through multiple mechanisms, immunotherapy should encompass multiple mechanisms to effectively counteract tumor-induced immune suppression. Based on the immune defects observed, strategies for active immunotherapy may include:

  • Restoring immune responsiveness by:
    • Correcting the DC maturation defect
    • Correcting the T-cell activation defect
    • Increasing the activity of NK cells
  • Counteracting tumor-induced immune suppression by:
    • Inhibiting T regulatory cells
    • Inhibiting the activity of immune checkpoints
    • Reducing the production of soluble immunosuppressive factors

The checkpoint inhibitors pembrolizumab and nivolumab are indicated for second-line therapy in patients with recurrent or metastatic SCCHN, demonstrating the importance of immunotherapy in SCCHN.

IRX-2 MECHANISM OF ACTION

IRX-2 is a proprietary therapeutic containing numerous active cytokine components, which restore and activate multiple immune cell types, including T cells, dendritic cells, and NK cells, that are able to recognize and destroy tumors.4-8 IRX-2 leads to an increase in tumor activation markers, including PD-L1,9 suggesting a complementary role with checkpoint inhibitors.

© 2017 IRX Therapeutics