Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies.

Delivery of Monomethyl Auristatin F to the Tumor Microenvironment with Noninternalizing Fibroblast Activation Protein-Cleavable Small Molecule-Drug Conjugates Elicits Potent Anticancer Activity.

OncoFAP is an ultrahigh affinity ligand of fibroblast activation protein (FAP), a tumor-associated antigen overexpressed in the stroma of the majority of solid tumors. OncoFAP has been previously implemented as a tumor-homing moiety for the development of small molecule drug conjugates (SMDCs). In the same context, the glycine--proline dipeptide was included with the aim to selectively undergo cleavage only in the presence of the target FAP, triggering the consequent release of the cytotoxic payload in the tumor microenvironment.

A single-chain variable fragment-based bispecific T-cell activating antibody against CD117 enables T-cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML-exclusive, non-HSPC-expressed cell-surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface-directed immunotherapy in this disease setting, time-limited combined immune-targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach.