A nanobody-stem cell platform targeting innate and adaptive immune axis in the tumour microenvironment.

ABSTRACT:

Background

Tumour associated macrophages (TAMs) and exhausted T cells are dominant in the immuno-suppressive tumour microenvironment (TME) and pose a challenge to effective cancer immunotherapy in solid tumours.

Methods

In this study, we immunised llamas and generated monovalent and biparatopic nanobodies (Nbs) against colony stimulating factor 1 receptor (CSF-1R) and programmed death receptor 1 (PD-1) to re-educate TAMs and overcome T cell exhaustion, respectively, in the TME. To circumvent short systemic half-life and low peak concentrations of Nbs in the TME, we developed a platform of allogenic off-the-shelf stem cells (SC) releasing biparatopic PD-1 and CSF-1R Nbs and tested its efficacy in different mouse models.

Findings

Nbs targeting CSF-1R and PD-1 inhibited

SUBMITTER: Vogiatzi I 

PROVIDER: S-EPMC12853783 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature