Preclinical studies with IRX-2 and thymosin alpha1 in combination therapy

Ann N Y Acad Sci. 2010 Apr:1194:162-8. doi: 10.1111/j.1749-6632.2010.05475.x.

Abstract

Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein with pleiotropic immune enhancing activity. IRX-2 is a primary cell-derived biologic containing multiple cytokines that enhance dendritic cell maturation, promote T-cell growth and differentiation, and inhibit tumor-mediated apoptosis of T cells. IRX-2 is being developed as an immunotherapeutic agent as a novel T-cell adjuvant platform for vaccines as well. Based on their biological activities, thymosin alpha1 and IRX-2 were predicted to exhibit synergistic effects when evaluated in animal and human studies. In animal studies, the combination of IRX-2 and Talpha1 (IRX-3) increased T-cell numbers compared to either alone during recovery from hydrocortisone mediated reduction. IRX-3 further enhanced reduction in tumor burden following chemotherapy compared to IRX-2. Based on these studies, IRX-3 is predicted to be especially important in a setting where reversal of immune suppression due to the presence of tumor, irradiation, and/or chemotherapy is likely to be an important factor in cytokine activity.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • T-Lymphocytes / metabolism
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / immunology
  • Thymosin / metabolism
  • Thymosin / pharmacology

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • IRX 2
  • Thymosin
  • Thymalfasin