A nanobody-guided multifunctional T cell engager promotes strong anti-tumor responses via synergistic immuno-photothermal effects

J Nanobiotechnology. 2024 Sep 14;22(1):561. doi: 10.1186/s12951-024-02781-1.

Abstract

Background: T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect.

Results: The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo.

Conclusions: Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic.

Keywords: Nanobody; Photothermal therapy; Solid tumor immunotherapy; T cell; T cell engager.

MeSH terms

  • Animals
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy* / methods
  • Indocyanine Green* / chemistry
  • Liposomes / chemistry
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Photothermal Therapy / methods
  • Single-Domain Antibodies* / chemistry
  • Single-Domain Antibodies* / immunology
  • T-Lymphocytes* / immunology

Substances

  • Single-Domain Antibodies
  • Indocyanine Green
  • Liposomes
  • CD3 Complex