A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8+ T cells in solid tumours

J Nanobiotechnology. 2024 Oct 19;22(1):645. doi: 10.1186/s12951-024-02914-6.

Abstract

Background: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions.

Results: The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts.

Conclusion: Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Keywords: Adoptive therapy; CD8+ T cell; CTLA-4; IL-12; Nanobody.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • CTLA-4 Antigen* / immunology
  • Cancer Vaccines* / immunology
  • Cell Fusion
  • Cell Line, Tumor
  • Dendritic Cells* / immunology
  • Female
  • Humans
  • Interleukin-12* / immunology
  • Mice
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology
  • Single-Domain Antibodies* / immunology
  • Single-Domain Antibodies* / pharmacology

Substances

  • Single-Domain Antibodies
  • Interleukin-12
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Recombinant Fusion Proteins
  • Antigens, Neoplasm