biostudies-literatureUnknown124Vogiatzi I<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>Nbs targeting CSF-1R and PD-1 inhibited EBioMedicine106122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12853783biostudies-literatureA nanobody-stem cell platform targeting innate and adaptive immune axis in the tumour microenvironment.PMC12853783Kanaya NVogiatzi ILee UJFarid ASShah KWakimoto HMoreno-Lama LRashidian MRossignoli FZwaenepoel OGettemans JLiu CLehmann AKajiwara YfalseA nanobody-stem cell platform targeting innate and adaptive immune axis in the tumour microenvironment.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>Nbs targeting CSF-1R and PD-1 inhibited 2026-01-01T00:00:00Z2026 Jan2026-06-10T09:00:18.432Z2026-06-10T03:11:23.255ZS-EPMC128537834154853710.1016/j.ebiom.2026.106122