Development and evaluation of a single domain antibody targeting folate receptor alpha for radioligand therapy.

Background: Folate receptor alpha (FRα) overexpression is seen in many cancers. Radioligand therapy (RLT) has emerged as a promising tool to target FRα and has been investigated previously, but further progression was limited due to high kidney retention and, subsequently, toxicity. To circumvent this, we present here the development of a [I]I-GMIB-conjugated anti-human FRα (hFRα) single-domain antibody (sdAb), with intrinsically fast renal clearance and concomitant low kidney retention.

Generic semi-automated radiofluorination strategy for single domain antibodies: [F]FB-labelled single domain antibodies for PET imaging of fibroblast activation protein-α or folate receptor-α overexpression in cancer.

Background: Radiofluorination of single domain antibodies (sdAbs) via N-succinimidyl-4-[F]fluorobenzoate ([F]SFB) has shown to be a promising strategy in the development of sdAb-based PET tracers. While automation of the prosthetic group (PG) [F]SFB production, has been successfully reported, no practical method for large scale sdAb labelling has been reported. Therefore, we optimized and automated the PG production, enabling a subsequently efficient manual conjugation reaction to an anti-fibroblast activation protein (FAP)-α sdAb (4AH29) and an anti-folate receptor (FR)-α sdAb (2BD42).

In vitro modelling of local gene therapy with IL-15/IL-15Rα and a PD-L1 antagonist in melanoma reveals an interplay between NK cells and CD4 T cells.

Blockade of the immune checkpoint axis consisting of programmed death-1 (PD-1) and its ligand PD-L1 alleviates the functional inhibition of tumor-infiltrating lymphoid cells yet weakly induces their expansion. Exogenous cytokines could further expand lymphoid cells and thus synergize with αPD-L1 therapy. However, systemic delivery of most cytokines causes severe toxicity due to unspecific expansion of immune cells in the periphery.

Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT.

Introduction: T cell Ig and ITIM domain receptor (TIGIT) is a next-generation immune checkpoint predominantly expressed on activated T cells and NK cells, exhibiting an unfavorable prognostic association with various malignancies. Despite the emergence of multiple TIGIT-blocking agents entering clinical trials, only a fraction of patients responded positively to anti-TIGIT therapy. Consequently, an urgent demand arises for noninvasive techniques to quantify and monitor TIGIT expression, facilitating patient stratification and enhancing therapeutic outcomes.