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Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist

Anti(α)-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy fails to provide durable clinical benefit for most patients with carcinoma. Recent studies suggested that strategies to reduce immunosuppressive cells, promote systemic T-cell responses and lymphocyte...

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First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach

First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active...

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Preclinical PET imaging of bispecific antibody ERY974 targeting CD3 and glypican 3 reveals that tumor uptake correlates to T cell infiltrate

Bispecific antibodies redirecting T cells to the tumor obtain increasing interest as potential cancer immunotherapy. ERY974, a full-length bispecific antibody targeting CD3ε on T cells and glypican 3 (GPC3) on tumors, has been in clinical development. However, information on the influence of T...

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Dual targeting of TGF-β and PD-L1 via a bifunctional anti-PD-L1/TGF-βRII agent: status of preclinical and clinical advances

A number of preclinical studies have shown bintrafusp alfa capable of (1) preventing or reverting TGF-β-induced epithelial-mesenchymal transition in human carcinoma cells; this alteration in tumor cell plasticity was shown to render human tumor cells more susceptible to immune-mediated attack as...

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Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples

Tumour-associated macrophages (TAMs) are often implicated in cancer progression but can also exert anti-tumour activities. Selective eradication of cancer-promoting (M2-like) TAM subsets is a highly sought-after goal. Here, the authors have devised a novel strategy to achieve selective TAM...