The present disclosure relates to methods and compositions comprising a universal cell delivery ligand configured to enhance the intratumoral delivery and distribution of therapeutic immune cells by facilitating their penetration through dense stroma surrounding tumor cells.

This disclosure relates to nanoparticles coated with fusion proteins comprising a domain that binds a cancer marker and a domain comprising a toxic polypeptide. In certain embodiments, the targeted cancer marker is urokinase plasminogen activator receptor (uPAR) insulin-like growth factor 1 receptor (IGF1R), EGFR, HER2, and/or other member of the ErbB family of receptors. In certain embodiments, the molecule that binds a cancer marker is an amino terminal fragment of uPA or variant capable of binding uPAR and/or IGF1 or variant capable of binding IGF1R. In certain embodiments, the toxic polypeptide is a bacterial exotoxin.

The present invention provides a fusion protein suitable for dissolving a fibrin clot and a pharmaceutical composition containing the fusion protein. According to the present invention, there is provided a fusion protein of an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a prourokinase mutant, in which amino acid sequence of a plasmin in a kringle domain is modified so as to be less cleavable with a plasmin, and a pharmaceutical composition containing the fusion protein.

Provided herein are methods for safe and effective thrombolysis in therapy for human subjects with symptoms of a potential stroke or acute myocardial infarction (AMI) using a sequential administration of a low dose bolus of human tissue plasminogen activator (tPA) followed by an infusion of a mutant form of human pro-urokinase (proUK).

There is provided a 177-Lu labelled peptide for site-specific targeting of the Urokinase Plasminogen Activator Receptor (uPAR) thereby enabling treatment of a cancer disease associated with high uPAR expression; e.g. treatment of colorectal cancer by administering to a patient an effective amount of the 177-Lu labelled peptide.

The present invention provides means and methods for treating MVT and associated and/or similar conditions. The invention therefore provides hybrid proteins for targeted delivery of plasminogen activators to platelet-VWF complexes, or alternatively to the site where these are located, in a fibrin-independent manner. The invention further provides therapeutic methods for conditions that can be prevented or treated by local delivery/stimulation of plasminogen activation to sites of microvascular occlusion.