The in vivo immunomodulatory and synergistic anti-tumor activity of thymosin α1-thymopentin fusion peptide and its binding to TLR2

Cancer Lett. 2013 Sep 1;337(2):237-47. doi: 10.1016/j.canlet.2013.05.006. Epub 2013 May 14.

Abstract

In the present study, the immunomodulatory and synergistic anti-tumor activity of thymosin α1-thymopentin fusion peptide (Tα1-TP5) was investigated in vivo. In addition, the potential receptor of Tα1-TP5 was investigated by surface plasmon resonance (SPR) binding studies. It was found that Tα1-TP5 (305 μg/kg) alleviated immunosuppression induced by hydrocortisone (HC). Tα1-TP5 (305 μg/kg) combined with cyclophosphamide (CY) had a better tumor growth inhibitory effect than CY alone. Furthermore, Tα1-TP5 had a higher affinity (KD=6.84 μmol/L) to toll-like receptor 2 (TLR2) than Tα1 (K(D)=35.4 μmol/L), but its affinity was not significantly different from that of TP5. The results of our present work indicate that Tα1-TP5 can possibly be developed as a new immunomodulatory agent.

Keywords: Immunoregulatory activity; Surface plasmon resonance; Synergistic anti-tumor activity; Thymosin α1–thymopentin; Toll-like receptor 2.

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Atrophy
  • B7-2 Antigen / metabolism
  • Cyclophosphamide / pharmacology
  • Drug Synergism
  • Histocompatibility Antigens Class I / metabolism
  • Hydrocortisone / pharmacology
  • Immunologic Factors / metabolism
  • Immunologic Factors / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / blood
  • Male
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protein Binding
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Surface Plasmon Resonance
  • Thymalfasin
  • Thymocytes / drug effects
  • Thymocytes / immunology
  • Thymocytes / pathology
  • Thymopentin / immunology
  • Thymopentin / metabolism
  • Thymopentin / pharmacology*
  • Thymosin / analogs & derivatives*
  • Thymosin / immunology
  • Thymosin / metabolism
  • Thymosin / pharmacology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology
  • Thymus Gland / pathology
  • Time Factors
  • Toll-Like Receptor 2 / metabolism*
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Histocompatibility Antigens Class I
  • Immunologic Factors
  • Immunosuppressive Agents
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Thymosin
  • Interferon-gamma
  • Cyclophosphamide
  • Thymopentin
  • Thymalfasin
  • Hydrocortisone